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39266184 | 500 | Current progress in CRISPR-Cas systems for cancer. | Cancer has been a primary contributor to morbidity and mortality worldwide. With an increasing trend of incidence and prevalence of cancer, progress has also been made in its treatment, starting from radiation and chemotherapy to immunotherapy and gene therapy. CRISPR-Cas technique, a promising gene editing tool, has been employed in cancer research for novel treatment regimens, identification of therapeutic targets, and unraveling the genetic mechanisms behind oncogenesis. CRISPR-based genome editing helped in identifying the roles of specific genetic factors linked to treatment resistance, metastasis, and cancer development. CRISPR allows the discovery of genes and treatment options through specifically interrupting tumor activators or activating tumor suppressor genes in cancer cells. Advancements in CRISPR technology, especially the use of immune cells like chimeric antigen receptor (CAR) T cells, has the potential to revolutionize personalized cancer treatment by precisely targeting and killing cancer cells. Furthermore, reactivating tumor suppressor genes makes cancer cells more susceptible to chemotherapy or immunotherapy. CRISPR-mediated genome editing can, hence, help to overcome resistance to traditional cancer treatments. The current manuscript covers that how is the CRISPR technology propelling revolutionary development in the field of cancer research, providing advance perspectives on the molecular causes of the disease and creating new lines for the development of more precise and potent cancer therapies. | [
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] | 2024-09-13 | 1 | 39266184 | [
"cancer cells",
"personalized cancer treatment",
"traditional cancer treatments",
"cancer development",
"cancer research",
"Cancer",
"cancer",
"tumor suppressor genes",
"treatment resistance",
"CRISPR technology",
"novel treatment regimens",
"treatment options",
"immune cells",
"genes",
"CRISPR",
"editing tool",
"specific genetic factors",
"revolutionary development",
"chimeric antigen receptor",
"CRISPR-based genome editing",
"therapeutic targets",
"new lines",
"advance perspectives",
"resistance",
"immunotherapy and gene therapy",
"chemotherapy",
"CAR) T cells",
"more precise and potent cancer therapies",
"CRISPR-Cas technique",
"the CRISPR technology"
] | [
"CAR-T",
"CRISPR-Cas",
"Cancer",
"Genome editing",
"Tumor"
] | 0 | 10.1016/bs.pmbts.2024.07.007 | [
"Fatima",
"Raja",
"Amir",
"Gul",
"Babar",
"Rajadas"
] | [
"Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan; Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.",
"Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan; Health Services Academy, Ministry of Health, Islamabad, Pakistan.",
"Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.",
"Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.",
"Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan; Advanced Drug Delivery and Regenerative Biomaterials Lab, Stanford University School of Medicine, Stanford University, Palo Alto, CA, United States. Electronic address: [email protected].",
"Advanced Drug Delivery and Regenerative Biomaterials Lab, Stanford University School of Medicine, Stanford University, Palo Alto, CA, United States. Electronic address: [email protected]."
] | [
"39266184"
] | [] | 9.533045 | 2.877111 |
39265193 | 501 | Therapeutic potentials of adoptive cell therapy in immune-mediated neuropathy. | Immune-mediated neuropathy (IMN) is a group of heterogenous neuropathies caused by intricate autoimmune responses. For now, known mechanisms of different IMN subtypes involve the production of autoantibodies, complement activation, enhanced inflammation and subsequent axonal/demyelinating nerve damages. Recent therapeutic studies mainly focus on specific antibodies and small molecule inhibitors previously approved in rheumatoid diseases. Initial strategies based on the pathophysiologic features of IMN should be explored. Adoptive cell therapy (ACT) refers to the emerging immunotherapies in which circulating immunocytes are collected from peripheral blood and modified with killing and immunomodulatory capacities. It consists of chimeric antigen receptor-T cell therapy, T cell receptor-engineered T cell, CAR-Natural killer cell therapy, and others. In the last decade, ACT has demonstrated extraordinary potentials in treating cancers, infectious diseases and autoimmune diseases. Versatile combinations of targets, chimeric domains and effector cells greatly empower ACT to treat complicated immune disorders. In this review, we summarized the advances of ACT and envisioned suitable strategies for different IMN subtypes. | [
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] | 2024-09-12 | 1 | 39265193 | [
"different IMN subtypes",
"Adoptive cell therapy",
"effector cells",
"ACT",
"IMN",
"small molecule inhibitors",
"autoimmune diseases",
"chimeric antigen receptor-T cell therapy",
"suitable strategies",
"infectious diseases",
"intricate autoimmune responses",
"specific antibodies",
"rheumatoid diseases",
"peripheral blood",
"enhanced inflammation",
"Initial strategies",
"Recent therapeutic studies",
"chimeric domains",
"complement activation",
"heterogenous neuropathies",
"circulating immunocytes",
"extraordinary potentials",
"complicated immune disorders",
"immunomodulatory capacities",
"Versatile combinations",
"subsequent axonal/demyelinating nerve damages",
"known mechanisms",
"autoantibodies",
"killing",
"cancers"
] | [
"Adoptive cell therapy",
"Autoimmune disease",
"Chimeric antigen receptor T cells",
"Immune-mediated neuropathy"
] | 0 | 10.1016/j.jaut.2024.103305 | [
"Shang",
"Zhao",
"Lin",
null
] | [
"Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; National Center for Neurological Disorders (NCND), Shanghai, China.",
"Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; National Center for Neurological Disorders (NCND), Shanghai, China.",
"Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; National Center for Neurological Disorders (NCND), Shanghai, China. Electronic address: [email protected].",
null
] | [
"39265193"
] | [] | 5.561634 | 6.592109 |
39263154 | 502 | Targeting TAG-72 in cutaneous T cell lymphoma. | Current monoclonal antibody-based treatment approaches for cutaneous T cell lymphoma (CTCL) rely heavily on the ability to identify a tumor specific target that is essentially absent on normal cells. Herein, we propose tumor associated glycoprotein-72 (TAG-72) as one such target. TAG-72 is a mucin-associated, truncated O-glycan that has been identified as a chimeric antigen receptor (CAR)-T cell target in solid tumor indications. To date, TAG-72 targeting has not been considered in the setting of hematological malignancies.
CD3
TAG-72 expression was significantly higher on total CD3
This study shows the first evidence of TAG-72 as a possible target for the treatment of CTCL. | [
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39262037 | 503 | Chimeric antigen receptor T-cell therapy for haematological malignancies: Insights from fundamental and translational research to bedside practice. | Autologous chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of lymphoid malignancies, leading to the approval of CD19-CAR T cells for B-cell lymphomas and acute leukaemia, and more recently, B-cell maturation antigen-CAR T cells for multiple myeloma. The long-term follow-up of patients treated in the early clinical trials demonstrates the possibility for long-term remission, suggesting a cure. This is associated with a low incidence of significant long-term side effects and a rapid improvement in the quality of life for responders. In contrast, other types of immunotherapies require prolonged treatments or carry the risk of long-term side effects impairing the quality of life. Despite impressive results, some patients still experience treatment failure or ultimately relapse, underscoring the imperative to improve CAR T-cell therapies and gain a better understanding of their determinants of efficacy to maximize positive outcomes. While the next-generation of CAR T cells will undoubtingly be more potent, there are already opportunities for optimization when utilizing the currently available CAR T cells. This review article aims to summarize the current evidence from clinical, translational and fundamental research, providing clinicians with insights to enhance their understanding and use of CAR T cells. | [
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] | 2024-09-12 | 1 | 39262037 | [
"CAR T cells",
"prolonged treatments",
"treatment failure",
"CD19-CAR T cells",
"significant long-term side effects",
"CAR T-cell therapies",
"long-term side effects",
"Autologous chimeric antigen receptor",
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"the currently available CAR T cells",
"patients",
"lymphoid malignancies",
"other types",
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"positive outcomes",
"acute leukaemia",
"more recently, B-cell maturation antigen-CAR T cells",
"impressive results",
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"lymphomas"
] | [
"CAR T‐cell",
"biomarkers",
"immunotherapy",
"leukaemia therapy",
"multiple myeloma",
"non‐Hodgkin's lymphoma"
] | 0 | 10.1111/bjh.19751 | [
"Grégoire",
"Coutinho de Oliveira",
"Caimi",
"Caers",
"Melenhorst"
] | [
"Center for ImmunoTherapy and Precision Immuno-Oncology (CITI), Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.\nDepartment of Clinical Hematology and Laboratory of Hematology (GIGA I3), University Hospital Center of Liège and University of Liège, Liège, Belgium.",
"Center for ImmunoTherapy and Precision Immuno-Oncology (CITI), Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.",
"Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA.",
"Department of Clinical Hematology and Laboratory of Hematology (GIGA I3), University Hospital Center of Liège and University of Liège, Liège, Belgium.",
"Center for ImmunoTherapy and Precision Immuno-Oncology (CITI), Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA."
] | [
"39262037"
] | [] | 7.058253 | 4.86485 |
39261906 | 504 | Updates on CAR T cell therapy in multiple myeloma. | Multiple myeloma (MM) is a hematological cancer characterized by the abnormal proliferation of plasma cells. Initial treatments often include immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs). Despite salient progress in diagnosis and treatment, most MM patients typically have a median life expectancy of only four to five years after starting treatment. In recent developments, the success of chimeric antigen receptor (CAR) T-cells in treating B-cell malignancies exemplifies a new paradigm shift in advanced immunotherapy techniques with promising therapeutic outcomes. Ide-cel and cilta-cel stand as the only two FDA-approved BCMA-targeted CAR T-cells for MM patients, a recognition achieved despite extensive preclinical and clinical research efforts in this domain. Challenges remain regarding certain aspects of CAR T-cell manufacturing and administration processes, including the lack of accessibility and durability due to T-cell characteristics, along with expensive and time-consuming processes limiting health plan coverage. Moreover, MM features, such as tumor antigen heterogeneity, antigen presentation alterations, complex tumor microenvironments, and challenges in CAR-T trafficking, contribute to CAR T-cell exhaustion and subsequent therapy relapse or refractory status. Additionally, the occurrence of adverse events such as cytokine release syndrome, neurotoxicity, and on-target, off-tumor toxicities present obstacles to CAR T-cell therapies. Consequently, ongoing CAR T-cell trials are diligently addressing these challenges and barriers. In this review, we provide an overview of the effectiveness of currently available CAR T-cell treatments for MM, explore the primary resistance mechanisms to these treatments, suggest strategies for improving long-lasting remissions, and investigate the potential for combination therapies involving CAR T-cells. | [
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10.1016/S2352-3026(22)00372-6 | [
"Nasiri",
"Asaadi",
"Mirzadeh",
"Abdolahi",
"Molaei",
"Gavgani",
"Rahbarizadeh"
] | [
"Department of Internal Medicine, College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.",
"Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.",
"Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.",
"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.",
"School of Medicine, Qom University of Medical Sciences, Qom, Iran.",
"Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran.",
"Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. [email protected].\nResearch and Development Center of Biotechnology, Tarbiat Modares University, Tehran, Iran. [email protected]."
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39261596 | 505 | Intracellular zinc protects tumours from T cell-mediated cytotoxicity. | Tumour immune evasion presents a significant challenge to the effectiveness of cancer immunotherapies. Recent advances in high-throughput screening techniques have uncovered that loss of antigen presentation and cytokine signalling pathways are central mechanisms by which tumours evade T cell immunity. To uncover additional vulnerabilities in tumour cells beyond the well-recognized antigen presentation pathway, we conducted a genome-wide CRISPR/Cas9 screen to identify genes that mediate resistance to chimeric-antigen receptor (CAR)-T cells, which function independently of classical antigen presentation. Our study revealed that loss of core-binding factor subunit beta (CBFβ) enhances tumour cell resistance to T cell killing, mediated through T cell-derived TNF. Mechanistically, RNA-sequencing and elemental analyses revealed that deletion of CBFβ disrupts numerous pathways including those involved in zinc homoeostasis. Moreover, we demonstrated that modulation of cellular zinc, achieved by supplementation or chelation, significantly altered tumour cell susceptibility to TNF by regulating the levels of inhibitor of apoptosis proteins. Consistent with this, treatment of tumour cells with a membrane-permeable zinc chelator had no impact on tumour cell viability alone, but significantly increased tumour cell lysis by CD8+ T cells in a TNF-dependent but perforin-independent manner. These results underscore the crucial role of intracellular zinc in regulating tumour cell susceptibility to T cell-mediated killing, revealing a novel vulnerability in tumour cells that might be exploited for the development of future cancer immunotherapeutics. | [
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] | 2024-09-12 | 33 | 39261596 | [
"tumour cells",
"tumour cell resistance",
"tumour cell susceptibility",
"tumour cell viability",
"T cell killing",
"T cell immunity",
"CAR)-T cells",
"CD8+ T cells",
"tumour cell lysis",
"tumours",
"Tumour immune evasion",
"antigen presentation",
"classical antigen presentation",
"intracellular zinc",
"cellular zinc",
"zinc homoeostasis",
"T cell-derived TNF",
"T cell-mediated killing",
"cytokine signalling pathways",
"numerous pathways",
"future cancer immunotherapeutics",
"TNF",
"additional vulnerabilities",
"cancer immunotherapies",
"CBFβ",
"loss",
"central mechanisms",
"resistance",
"Recent advances",
"apoptosis proteins"
] | [] | 0 | 10.1038/s41418-024-01369-4 | [
"Lelliott",
"Naddaf",
"Ganio",
"Michie",
"Wang",
"Liu",
"Silke",
"Ahn",
"Ramsbottom",
"Brennan",
"Freeman",
"Goel",
"Vervoort",
"Kearney",
"Beavis",
"McDevitt",
"Silke",
"Oliaro"
] | [
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia. [email protected].\nSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia. [email protected].\nOlivia Newton-John Cancer Research Institute, Heidelberg, VIC, 3084, Australia. [email protected].",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.\nSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.",
"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, 3010, Australia.",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.",
"Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.",
"Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.",
"Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.\nSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.\nSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.\nSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.\nSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.\nSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.",
"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, 3010, Australia.",
"Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.\nDepartment of Medical Biology, The University of Melbourne, Parkville, VIC, 3010, Australia.",
"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia. [email protected].\nSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia. [email protected]."
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] | [] | 10.713982 | 5.113009 |
39258858 | 506 | How can we improve the successful identification of patients suitable for CAR-T cell therapy? | In recent years, chimeric antigen receptor T (CAR-T) cell therapy has resulted in a breakthrough in the treatment of patients with refractory or relapsed hematological malignancies. However, the identification of patients suitable for CAR-T cell therapy needs to be improved.
CAR-T cell therapy has demonstrated excellent efficacy in hematological malignancies; however, views on determining when to apply CAR-T cells in terms of the evaluation of patient characteristics remain controversial.
We reviewed the current feasibility and challenges of CAR-T cell therapy in the most common hematological malignancies and classified them according to the disease type and treatment priority, to guide clinicians and researchers in applying and investigating CAR-T cells furtherly. | [
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] | 2024-09-11 | 1 | 39258858 | [
"hematological malignancies",
"CAR-T cell therapy",
"CAR-T cells",
"patient characteristics",
"excellent efficacy",
"refractory or relapsed hematological malignancies",
"patients",
"recent years",
"challenges",
"terms",
"clinicians",
"researchers",
"CAR-T",
"the most common hematological malignancies",
"the disease type and treatment priority",
"the current feasibility",
"the treatment",
"the evaluation",
"a breakthrough",
"the identification",
"We",
"them"
] | [
"Chimeric antigen receptor T cell",
"hematological malignancy",
"lymphoblastic leukemia",
"multiple myeloma",
"non-Hodgkin lymphoma"
] | 0 | 10.1080/14737159.2024.2399152 | [
"Feng",
"Wu",
"Gu",
"Hu",
"Huang"
] | [
"Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.\nLiangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.\nInstitute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.\nZhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China.",
"Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.\nLiangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.\nInstitute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.\nZhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China.",
"Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.\nLiangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.\nInstitute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.\nZhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China.",
"Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.\nLiangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.\nInstitute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.\nZhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China.",
"Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.\nInstitute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.\nZhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China."
] | [
"39258858"
] | [] | 7.751433 | 4.056729 |
39257746 | 507 | Spatiotemporal dynamics of tumor - CAR T-cell interaction following local administration in solid cancers. | The success of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic malignancies has generated widespread interest in translating this technology to solid cancers. However, issues like tumor infiltration, the immunosuppressive tumor microenvironment, and tumor heterogeneity limit its efficacy in the solid tumor setting. Recent experimental and clinical studies propose local administration directly into the tumor or at the tumor site to increase CAR T-cell infiltration and improve treatment outcomes. Characteristics of the types of solid tumors that may be the most receptive to this treatment approach remain unclear. In this work, we develop a spatiotemporal model for CAR T-cell treatment of solid tumors, and use numerical simulations to compare the effect of introducing CAR T cells via intratumoral injection versus intracavitary administration in diverse cancer types. We demonstrate that the model can recapitulate tumor and CAR T-cell data from imaging studies of local administration of CAR T cells in mouse models. Our results suggest that locally administered CAR T cells will be most successful against slowly proliferating, highly diffusive tumors, which have the lowest average tumor cell density. These findings affirm the clinical observation that CAR T cells will not perform equally across different types of solid tumors, and suggest that measuring tumor density may be helpful when considering the feasibility of CAR T-cell therapy and planning dosages for a particular patient. We additionally find that local delivery of CAR T cells can result in deep tumor responses, provided that the initial CAR T-cell dose does not contain a significant fraction of exhausted cells. | [
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] | 2024-09-11 | 74 | 39257746 | [
"CAR T cells",
"solid tumors",
"tumor infiltration",
"exhausted cells",
"tumor density",
"tumor",
"tumor heterogeneity",
"deep tumor responses",
"CAR T-cell treatment",
"CAR T-cell therapy",
"CAR T-cell infiltration",
"CAR T-cell data",
"the lowest average tumor cell density",
"solid cancers",
"local administration",
"the initial CAR T-cell dose",
"CAR) T-cell therapy",
"locally administered CAR T cells",
"the solid tumor setting",
"intracavitary administration",
"diverse cancer types",
"local delivery",
"the immunosuppressive tumor microenvironment",
"different types",
"treatment outcomes",
"the tumor site",
"mouse models",
"chimeric antigen receptor",
"widespread interest",
"hematologic malignancies"
] | [] | 0 | 10.1101/2024.08.29.610392 | [
"Owens",
"Rahman",
"Bozic"
] | [
"Department of Applied Mathematics, University of Washington, Seattle WA.\nFred Hutchinson Cancer Center, Seattle WA.",
"Fred Hutchinson Cancer Center, Seattle WA.\nArtificial Intelligence Institute in Dynamic Systems, University of Washington, Seattle WA.",
"Department of Applied Mathematics, University of Washington, Seattle WA.\nFred Hutchinson Cancer Center, Seattle WA."
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39256765 | 508 | Non-viral approaches in CAR-NK cell engineering: connecting natural killer cell biology and gene delivery. | Natural Killer (NK) cells are exciting candidates for cancer immunotherapy with potent innate cytotoxicity and distinct advantages over T cells for Chimeric Antigen Receptor (CAR) therapy. Concerns regarding the safety, cost, and scalability of viral vectors has ignited research into non-viral alternatives for gene delivery. This review comprehensively analyses recent advancements and challenges with non-viral genetic modification of NK cells for allogeneic CAR-NK therapies. Non-viral alternatives including electroporation and multifunctional nanoparticles are interrogated with respect to CAR expression and translational responses. Crucially, the link between NK cell biology and design of drug delivery technologies are made, which is essential for development of future non-viral approaches. This review provides valuable insights into the current state of non-viral CAR-NK cell engineering, aimed at realising the full potential of NK cell-based immunotherapies. | [
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39255722 | 509 | EphA2 specific chimeric antigen receptor engineered T cells for the treatment of prostate cancer. | Erythropoietin-producing hepatocyte receptor A2 (EphA2) is an attractive target for immunotherapy due to its high expression in a variety of solid tumors including prostate cancer. Among various types of immunotherapeutics, chimeric antigen receptor T (CAR-T) cell therapy has made promising progress in hematological and solid tumors. Here, we detected the expression of EphA2 in prostate cancer cells and developed a second-generation CAR targeting EphA2 with CD28 as a co-stimulatory receptor to explore its tumor suppressive potential for prostate cancer in vitro and in vivo. EphA2 was highly expressed on the surface of PC3 and DU145 cells. EphA2 CART cells effectively inhibited prostate cancer growth in an antigen-dependent manner in vitro and in vivo. In addition, tumor cells could stimulate the proliferation of CAR-T cells and the release of cytokine IFN-γ in vitro. These findings shed light on EphA2 as a potential target for prostate cancer, promising EphA2 specific CAR-T cells for the treatment of prostate cancer. | [
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] | 2024-09-11 | 27 | 39255722 | [
"prostate cancer cells",
"EphA2 CART cells",
"tumor cells",
"prostate cancer",
"prostate cancer growth",
"DU145 cells",
"EphA2",
"solid tumors",
"EphA2 specific CAR-T cells",
"CAR-T cells",
"promising progress",
"CAR",
"a co-stimulatory receptor",
"various types",
"Erythropoietin-producing hepatocyte receptor",
"hematological and solid tumors",
"its tumor suppressive potential",
"A2",
"immunotherapeutics",
"CD28",
"vivo",
"immunotherapy",
"second",
"PC3",
"light",
"IFN",
"CAR-T",
"DU145",
"an attractive target",
"a potential target"
] | [
"Chimeric antigen receptor (CAR)",
"EphA2",
"Immunotherapy",
"Prostate cancer"
] | 0 | 10.1016/j.tranon.2024.102111 | [
"Zhang",
"Wang",
"Wang",
"Zhang",
"Li",
"Ma",
"Zheng",
"Wang",
"Li"
] | [
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: [email protected].",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: [email protected]."
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] | [] | 9.760437 | 6.638194 |
39255444 | 510 | STRIvE-02: A First-in-Human Phase I Study of Systemically Administered B7-H3 Chimeric Antigen Receptor T Cells for Patients With Relapsed/Refractory Solid Tumors. | B7-H3 is an immunoregulatory protein overexpressed by many pediatric solid tumors with limited expression on critical organs, making it an attractive immunotherapy target. We present a first-in-human phase I clinical trial systemically administered B7-H3 chimeric antigen receptor (CAR) T cells for young patients with relapsed or refractory solid tumors.
Patients were enrolled onto a phase I trial to examine the safety of B7-H3-specific CARs at various dose levels (DLs) using a standard 3 + 3 dose escalation design.
Sixteen patients (range, 11-24 years; median, 18.5 years) were enrolled, and nine were treated at DL1 (0.5 × 10
B7-H3 CAR T cells are tolerable and demonstrate limited antitumor activity without acute on-target, off-tumor toxicity. High levels of CAR T cell expansion may be necessary to achieve objective responses, but undefined host and tumor microenvironment factors appear to be critical (ClinicalTrials.gov identifier: NCT04483778). | [
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] | 2024-09-10 | 1 | 39255444 | [
"CAR T cell expansion",
"T cells",
"many pediatric solid tumors",
"tumor",
"critical organs",
"various dose levels",
"young patients",
"limited antitumor activity",
"CAR",
"B7-H3 chimeric antigen receptor",
"limited expression",
"objective responses",
"undefined host and tumor microenvironment factors",
"High levels",
"Patients",
"relapsed or refractory solid tumors",
"target",
"B7-H3",
"10\nB7-H3 CAR T cells",
"B7-H3-specific CARs",
"DL1",
"×",
"human",
"median",
"first",
"range",
"NCT04483778",
"an immunoregulatory protein",
"Sixteen patients",
"a phase"
] | [] | 0 | 10.1200/JCO.23.02229 | [
"Pinto",
"Albert",
"Taylor",
"Ullom",
"Wilson",
"Huang",
"Wendler",
"Pattabhi",
"Seidel",
"Brown",
"Gustafson",
"Rawlings-Rhea",
"Cheeney",
"Burleigh",
"Gustafson",
"Orentas",
"Vitanza",
"Gardner",
"Jensen",
"Park"
] | [
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.\nBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA.",
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.\nBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA.",
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.\nBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA.",
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.",
"Seattle Children's Therapeutics, Seattle, WA.",
"Seattle Children's Therapeutics, Seattle, WA.",
"Seattle Children's Therapeutics, Seattle, WA.",
"Seattle Children's Therapeutics, Seattle, WA.",
"Seattle Children's Therapeutics, Seattle, WA.",
"Seattle Children's Therapeutics, Seattle, WA.",
"Seattle Children's Therapeutics, Seattle, WA.",
"Seattle Children's Therapeutics, Seattle, WA.",
"Department of Radiology, Seattle Children's Hospital, University of Washington, Seattle, WA.",
"Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA.",
"Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA.",
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.\nBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA.",
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.\nBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA.",
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.\nBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA.",
"Seattle Children's Therapeutics, Seattle, WA.",
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.\nBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA."
] | [
"39255444"
] | [] | 10.081314 | 6.636034 |
39253082 | 511 | Potential of gamma/delta T cells for solid tumor immunotherapy. | Gamma/delta T (γδ T)cells possess a unique mechanism for killing tumors, making them highly promising and distinguished among various cell therapies for tumor treatment. This review focuses on the major histocompatibility complex (MHC)-independent recognition of antigens and the interaction between γδ T cells and solid tumor cells. A comprehensive review is provided regarding the classification of human gamma-delta T cell subtypes, the characteristics and mechanisms underlying their functions, as well as their r545egulatory effects on tumor cells. The involvement of γδ T cells in tumorigenesis and migration was also investigated, encompassing potential therapeutic targets such as apoptosis-related molecules, the TNF receptor superfamily member 6(FAS)/FAS Ligand (FASL) pathways, butyrophilin 3A-butyrophilin 2A1 (BTN3A-BTN2A1) complexes, and interactions with CD4, CD8, and natural killer (NK) cells. Additionally, immune checkpoint inhibitors such as programmed cell death protein 1/Programmed cell death 1 ligand 1 (PD-1/PD-L1) have the potential to augment the cytotoxicity of γδ T cells. Moreover, a review on gamma-delta T cell therapy products and their corresponding clinical trials reveals that chimeric antigen receptor (CAR) gamma-delta T therapy holds promise as an approach with encouraging preclinical outcomes. However, practical issues pertaining to manufacturing and clinical aspects need resolution, and further research is required to investigate the long-term clinical side effects of CAR T cells. In conclusion, more comprehensive studies are necessary to establish standardized treatment protocols aimed at enhancing the quality of life and survival rates among tumor patients utilizing γδ T cell immunotherapy. | [
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] | [] | 10.275542 | 4.356795 |
39252592 | 512 | IL23R-specific CAR Tregs for the treatment of Crohn's disease. | Regulatory T cells (Tregs) are key regulators in maintaining tissue homeostasis. Disrupted immune homeostasis is associated with Crohn's disease (CD) pathogenesis. Thus, Treg therapy represents a promising long-acting treatment to restore immune balance in the diseased intestine. CAR (Chimeric Antigen Receptor) T-cell therapy has revolutionized cancer treatment. This innovative approach also provides the opportunity to improve therapy for CD. By targeting a disease-relevant protein, Interleukin-23 receptor (IL23R), we engineered Tregs expressing IL23R-CAR for treating active CD.
Intestinal IL23R expression from active CD was verified by immunohistochemical analysis. Phenotypic and functional characteristics of IL23R-CAR Tregs were assessed using in vitro assays and their migration capacity was monitored in a xenograft tumor model. Transcriptomic and proteomic analyses were performed to associate molecular profiles with IL23R-CAR Treg activation against colon biopsy-derived cells from active CD patients.
Our study showed that IL23R-CAR displayed negligible tonic signalling and strong signal-to-noise ratio. IL23R-CAR Tregs maintained regulatory phenotype during in vitro expansion, even when chronically exposed to proinflammatory cytokines and target antigen. IL23R engagement on IL23R-CAR Tregs triggered CAR-specific activation and significantly enhanced their suppressive activity. Also, IL23R-CAR Tregs migrated to IL23R-expressing tissue in humanized mice. Finally, IL23R-CAR Tregs elicited a specific activation against colon biopsy-derived cells from active CD, suggesting an efficient CAR engagement in active CD. Molecular profiling of CD patient biopsies also revealed transcriptomic and proteomic patterns associated with IL23R-CAR activation.
Overall, our results demonstrate that IL23R-CAR Tregs represent a promising therapy for active CD. | [
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] | 2024-09-10 | 1 | 39252592 | [
"Treg therapy",
"active CD",
"active CD patients",
"CD patient biopsies",
"Treg",
"Tregs",
"IL23R engagement",
"Regulatory T cells",
"IL23R-CAR Tregs",
"IL23R",
"IL23R-CAR Treg activation",
"Disrupted immune homeostasis",
"IL23R-CAR Treg",
"therapy",
"immune balance",
"tissue homeostasis",
"IL23R-CAR",
"IL23R-CAR activation",
"regulatory phenotype",
"colon biopsy-derived cells",
"proinflammatory cytokines",
"negligible tonic",
"vitro expansion",
"molecular profiles",
"cancer treatment",
"Chimeric Antigen Receptor",
"Interleukin-23 receptor",
"CAR-specific activation",
"key regulators",
"immunohistochemical analysis"
] | [
"CAR-Treg",
"Crohn’s disease",
"IBD",
"IL23R",
"cell therapy"
] | 0 | 10.1093/ecco-jcc/jjae135 | [
"Cui",
"David",
"Bouchareychas",
"Rouquier",
"Sajuthi",
"Ayrault",
"Navarin",
"Lara",
"Lafon",
"Saviane",
"Boulakirba",
"Menardi",
"Demory",
"Frikeche",
"de la Forest Divonne Beghelli",
"Lu",
"Dumont",
"Abel",
"Fenard",
"de la Rosa",
"Gertner-Dardenne"
] | [
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Bioinformatics, Sangamo Therapeutics, Richmond, CA, USA.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Bioinformatics, Sangamo Therapeutics, Richmond, CA, USA.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France.",
"Research, Sangamo Therapeutics, Valbonne, France."
] | [
"39252592"
] | [] | 7.940292 | 5.181811 |
39251462 | 513 | CAR T cell therapy for pediatric central nervous system tumors: a review of the literature and current North American trials. | Central nervous system (CNS) tumors are the leading cause of cancer-related death in children. Typical therapy for CNS tumors in children involves a combination of surgery, radiation, and chemotherapy. While upfront therapy is effective for many high-grade tumors, therapy at the time of relapse remains limited. Furthermore, for diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG), there are currently no curative therapies. Chimeric antigen receptor T (CAR T) cell therapy is a promising novel treatment avenue for these tumors. Here, we review the preclinical evidence for CAR T cell use in pediatric brain tumors, the preliminary clinical experience of CNS CAR T cell trials, toxicity associated with systemic and locoregional CAR T cell therapy for CNS tumors, challenges in disease response evaluation with CAR T cell therapy, and the knowledge gained from correlative biologic studies from these trials in the pediatric and young adult population. | [
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"CAR T cell therapy",
"CNS CAR T cell trials",
"CAR T cell use",
"CNS tumors",
"pediatric brain tumors",
"upfront therapy",
"therapy",
"Typical therapy",
"systemic and locoregional CAR T cell therapy",
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"challenges",
"relapse",
"a promising novel treatment avenue",
"toxicity",
"radiation",
"cancer-related death",
"the preliminary clinical experience"
] | [
"Cancer",
"Central nervous system",
"Chimeric antigen receptor",
"Immunotherapy",
"Pediatric"
] | 0 | 10.1007/s10555-024-10208-4 | [
"Ronsley",
"Bertrand",
"Song",
"Timpanaro",
"Choe",
"Tlais",
"Vitanza",
"Park"
] | [
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.\nBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.",
"Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN, 38105, USA.\nDivision of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.",
"Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.",
"Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.",
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.\nClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.",
"Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN, 38105, USA.\nDivision of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.",
"Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.\nBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.",
"Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN, 38105, USA. [email protected]."
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] | [] | 9.876373 | 7.191321 |
39251182 | 514 | The Pluripotent Path to Immunotherapy. | Adoptive cell therapy (ACT) enhances the patient's own immune cells' ability to identify and eliminate cancer cells. Several immune cell types are currently being applied in autologous ACT, including T cells, natural killer (NK) cells, and macrophages. The cells' inherent antitumor capacity can be used, or they can be targeted toward tumor-associated antigen through expression of a chimeric antigen receptor (CAR). Although CAR-based ACT has achieved great results in hematologic malignancies, the accessibility of ACT is limited by the autologous nature of the therapy. Induced pluripotent stem cells (iPSCs) hold the potential to address this challenge, because they can provide an unlimited source for the in vitro generation of immune cells. Various immune subsets have been generated from iPSC for application in ACT, including several T-cell subsets (αβT cells, mucosal-associated invariant T cells, invariant NKT [iNKT] cells, and γδT cells), as well as NK cells, macrophages, and neutrophils. iPSC-derived αβT, NK, and iNKT cells are currently being tested in phase I clinical trials. The ability to perform (multiplexed) gene editing at the iPSC level and subsequent differentiation into effector populations not only expands the arsenal of ACT but allows for development of ACT utilizing cell types which cannot be efficiently obtained from peripheral blood or engineered and expanded in vitro. | [
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] | 2024-09-10 | 1 | 39251182 | [
"immune cells",
"T cells",
"cell types",
"NK cells",
"Several immune cell types",
"iNKT cells",
"cancer cells",
"Adoptive cell therapy",
"Induced pluripotent stem cells",
"autologous ACT",
"ACT",
"mucosal-associated invariant T cells",
"several T-cell subsets",
"Various immune subsets",
"NK) cells",
"αβT cells",
"γδT cells",
"subsequent differentiation",
"effector populations",
"great results",
"hematologic malignancies",
"The cells inherent antitumor capacity",
"peripheral blood",
"CAR-based ACT",
"the patients own immune cells ability",
"natural killer",
"NK",
"macrophages",
"tumor-associated antigen",
"iPSCs"
] | [] | 0 | 10.1016/j.exphem.2024.104648 | [
"Diop",
"van der Stegen"
] | [
"Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY.",
"Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: [email protected]."
] | [
"39251182"
] | [] | 9.611932 | 4.323605 |
39245925 | 515 | Biodegradable nanoplatforms for antigen delivery: part II - nanoparticles, hydrogels, and microneedles for cancer immunotherapy. | In recent years, chimeric antigen receptor T (CAR-T) cell therapy has resulted in a breakthrough in the treatment of patients with refractory or relapsed hematological malignancies. However, the identification of patients suitable for CAR-T cell therapy needs to be improved.
CAR-T cell therapy has demonstrated excellent efficacy in hematological malignancies; however, views on determining when to apply CAR-T cells in terms of the evaluation of patient characteristics remain controversial.
We reviewed the current feasibility and challenges of CAR-T cell therapy in the most common hematological malignancies and classified them according to disease type and treatment priority, to guide clinicians and researchers in applying and investigating CAR-T cells further. | [
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] | 2024-09-09 | 1 | 39245925 | [
"hematological malignancies",
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"CAR-T cells",
"patient characteristics",
"excellent efficacy",
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"patients",
"recent years",
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"We",
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] | [
"Cancer immunotherapy",
"antigen delivery",
"hydrogels",
"microneedles",
"polymeric nanoparticles"
] | 0 | 10.1080/17425247.2024.2400291 | [
"Burgos",
"Vega",
"García",
"Pujol",
"Sánchez-López",
"Souto"
] | [
"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.",
"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.\nInstitute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain.",
"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.\nInstitute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain.",
"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.\nInstitute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain.",
"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.\nInstitute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain.",
"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.\nUCD School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin, Ireland."
] | [
"39245925"
] | [] | 7.770274 | 4.035891 |
39245737 | 516 | Advances on immunotherapy for osteosarcoma. | Osteosarcoma is the most common primary bone cancer in children and young adults. Limited progress has been made in improving the survival outcomes in patients with osteosarcoma over the past four decades. Especially in metastatic or recurrent osteosarcoma, the survival rate is extremely unsatisfactory. The treatment of osteosarcoma urgently needs breakthroughs. In recent years, immunotherapy has achieved good therapeutic effects in various solid tumors. Due to the low immunogenicity and immunosuppressive microenvironment of osteosarcoma, immunotherapy has not yet been approved in osteosarcoma patients. However, immune-based therapies, including immune checkpoint inhibitors, chimeric antigen receptor T cells, and bispecfic antibodies are in active clinical development. In addition, other immunotherapy strategies including modified-NK cells/macrophages, DC vaccines, and cytokines are still in the early stages of research, but they will be hot topics for future study. In this review, we showed the functions of cell components including tumor-promoting and tumor-suppressing cells in the tumor microenvironment of osteosarcoma, and summarized the preclinical and clinical research results of various immunotherapy strategies in osteosarcoma, hoping to provide new ideas for future research in this field. | [
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10.1158/1078-0432.CCR-16-2138 | [
"Yu",
"Yao"
] | [
"Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.",
"Center for Joint Surgery, Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. [email protected]."
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39244642 | 517 | Autologous CD7 CAR-T cells generated without T cell pre-selection in pediatric patients with relapsed/refractory T-ALL: A phase I trial. | Chimeric antigen receptor (CAR)-T cell therapy showed preliminary activity in patients with refractory or relapsed T cell acute lymphoblastic leukemia (r/r T-ALL). However, many obstacles remain, including manufacturing difficulties and risk of infections. This phase I study (NCT04840875) evaluated autologous CD7 CAR-T cells manufactured without pre-selection of healthy T cells in r/r T-ALL. Thirty patients (29 children and one adult) with a median of two lines of prior therapy but without detectable peripheral leukemia were enrolled. Excluding three cases of manufacturing failures, a total of 27 (90%) patients received infusions after products were confirmed free of leukemia contamination, including 16 (59%) meeting planned target doses. Common adverse events within 30 days included grade 3-4 cytopenias (100%), grade 1-2 (70%) and 3-4 (7%, including one dose-limiting toxicity) cytokine release syndrome, grade 1 neurotoxicity (7%), grade 2 infection (4%), and grade 2 graft-versus-host disease (4%). Two patients developed grade 2 infections after day 30. At day 30, 96% responded and 85% achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi). Seventy-four percent underwent transplantation. Twelve-month progression-free survival with and without censoring transplantation was 22% (95% confidence interval 4%-100%) and 57% (41%-81%), respectively. These results support that autologous CD7 CAR-T therapy without T cell pre-selection is feasible in patients with r/r T-ALL. | [
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] | 2024-09-08 | 1 | 39244642 | [
"CAR)-T cell therapy",
"patients",
"detectable peripheral leukemia",
"prior therapy",
"leukemia contamination",
"grade",
"autologous CD7 CAR-T cells",
"autologous CD7 CAR-T therapy",
"relapsed T cell acute lymphoblastic leukemia",
"95% confidence interval",
"incomplete hematologic recovery",
"censoring transplantation",
"planned target doses",
"CR",
"T cell pre",
"complete remission",
"manufacturing failures",
"infections",
"Common adverse events",
"Chimeric antigen receptor",
"day",
"healthy T cells",
"100%",
"22%",
"4%",
"4%-100%",
"41%-81%",
"57%",
"59%",
"7%"
] | [
"CAR-T",
"CD7",
"T cell acute lymphoblastic leukemia",
"T cell pre-selection",
"safety",
"stem cell transplantation"
] | 0 | 10.1016/j.ymthe.2024.09.006 | [
"Zhao",
"Li",
"Zuo",
"Han",
"Deng",
"Ling",
"Zhang",
"Peng",
"Xu",
"Duan",
"Wang",
"Yu",
"Zheng",
"Xu",
"Yuan",
"Tian",
"Tang",
"Zhang",
"Niu",
"Zhang",
"Chang",
"Luo",
"Feng",
"Pan"
] | [
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China; Department of Hematology, Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Beijing Gobroad Boren Hospital, Beijing 100070, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China.",
"Cytology Laboratory, Beijing GoBroad Boren Hospital, Beijing 100070, China.",
"Department of Hematology, Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Beijing Gobroad Boren Hospital, Beijing 100070, China.",
"Shanghai YaKe Biotechnology Ltd., Shanghai 200438, China.",
"Shanghai YaKe Biotechnology Ltd., Shanghai 200438, China.",
"Department of Hematology, Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Beijing Gobroad Boren Hospital, Beijing 100070, China.",
"Department of Hematology, Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Beijing Gobroad Boren Hospital, Beijing 100070, China.",
"Department of Hematology, Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Beijing Gobroad Boren Hospital, Beijing 100070, China.",
"Medical Laboratory, Beijing GoBroad Boren Hospital, Beijing 100070, China.",
"Medical Laboratory, Beijing GoBroad Boren Hospital, Beijing 100070, China.",
"Medical Laboratory, Beijing GoBroad Boren Hospital, Beijing 100070, China.",
"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Austin, TX 77030, USA.",
"Gobroad Research Center, GoBroad Medical Group, Beijing 100070, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China.",
"Department of Hospital Management, GoBroad Medical Group, Beijing 100070, China.",
"Shanghai YaKe Biotechnology Ltd., Shanghai 200438, China; Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200438, China.",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China. Electronic address: [email protected].",
"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China; Central laboratory, Fujian Medical Union Hospital, Fuzhou 350001, China; CAMS Key Laboratory for Prevention and Control of Hematological Disease Treatment Related Infection, Tianjin 300020, China. Electronic address: [email protected].",
"Department of Hematology, Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Beijing Gobroad Boren Hospital, Beijing 100070, China. Electronic address: [email protected]."
] | [
"39244642"
] | [] | 6.482115 | 5.867164 |
39243430 | 518 | Optimization of anti-TIM3 chimeric antigen receptor with CD8α spacer and TNFR-based costimulation for enhanced efficacy in AML therapy. | CAR T cell therapy for AML remains limited due to the lack of a proper target without on-target off-tumor toxicity. TIM3 is a promising target due to its high expression on AML cells and absence in most normal hematopoietic cells. Previous reports have shown that each CAR component impacts CAR functionality. Here, we optimized TIM-3 targeting CAR T cells for AML therapy. We generated CARs targeting TIM3 with two different non-signaling domains: an IgG2-CH3 spacer with CD28 transmembrane domain (CH3/CD28) and a CD8α spacer with CD8α transmembrane domain (CD8/CD8), and evaluated their characteristics and function. Incorporating the non-signaling CH3/CD28 domain resulted in unstable CAR expression in anti-TIM3 CAR T cells, leading to lower surface CAR expression over time and reduced cytotoxic function compared to anti-TIM3 CARs with the CD8/CD8 domain. Both types of anti-TIM3 CAR T cells transiently exhibited fratricide, which subsided overtime, and both CAR T cells achieved substantial T cell expansion. To further optimize the design, we explored the effects of different costimulatory domains. Compared with CD28 costimulation, 4-1BB and CD27 combined with a CD8/CD8 non-signaling domain showed higher cytokine secretion, superior antitumor activity, and enhanced T-cell persistence after repeated antigen exposure. These findings emphasize the impact of the optimal design of CAR constructs that provide efficient function. In the context of anti-TIM3 CAR T cells, using a CD8α spacer and transmembrane domain with TNFR-based costimulation is a promising CAR design to improve anti-TIM3 CAR T cell function for AML therapy. | [
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] | 2024-09-07 | 1 | 39243430 | [
"anti-TIM3 CAR T cells",
"anti-TIM3 CAR T cell function",
"CAR T cells",
"CAR T cell therapy",
"anti-TIM3 CARs",
"substantial T cell expansion",
"AML cells",
"unstable CAR expression",
"lower surface CAR expression",
"CD28 transmembrane domain",
"CD8α transmembrane domain",
"most normal hematopoietic cells",
"CAR functionality",
"CAR",
"CARs",
"transmembrane domain",
"CAR constructs",
"different costimulatory domains",
"both CAR T cells",
"two different non-signaling domains",
"AML therapy",
"reduced cytotoxic function",
"CD28 costimulation",
"a CD8/CD8 non-signaling domain",
"higher cytokine secretion",
"efficient function",
"superior antitumor activity",
"enhanced T-cell persistence",
"the non-signaling CH3/CD28 domain",
"target"
] | [
"41BB",
"AML",
"CAR T Cell",
"CD27",
"Non-signaling domain",
"TIM3"
] | 0 | 10.1016/j.biopha.2024.117388 | [
"Pe",
"Jewmoung",
"Rad",
"Chantarat",
"Chanswangphuwana",
"Tashiro",
"Suppipat",
"Tawinwung"
] | [
"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.",
"Cellular Immunotherapy Research Unit, Chulalongkorn University, Bangkok, Thailand.",
"Kite Pharma Inc, Santa Monica, California, USA.",
"Cellular Immunotherapy Research Unit, Chulalongkorn University, Bangkok, Thailand.",
"Division of Hematology, Department of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.",
"Department of Hematology/Oncology, Teikyo University School of Medicine, Tokyo, Japan.",
"Cellular Immunotherapy Research Unit, Chulalongkorn University, Bangkok, Thailand; Department of Research Affair, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Thailand Hub of Talents in Cancer Immunotherapy (TTCI), Bangkok, Thailand.",
"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; Cellular Immunotherapy Research Unit, Chulalongkorn University, Bangkok, Thailand; Thailand Hub of Talents in Cancer Immunotherapy (TTCI), Bangkok, Thailand. Electronic address: [email protected]."
] | [
"39243430"
] | [] | 8.056113 | 6.017865 |
39243425 | 519 | Astragalus polysaccharide enhances antitumoral effects of chimeric antigen receptor- engineered (CAR) T cells by increasing CD122 | Chimeric antigen receptor-engineered T (CAR-T) cell therapy of cancer has been a hotspot and promising. However, due to rapid exhaustion, CAR-T cells are less effective in solid tumors than in hematological ones. CD122 | [
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] | 2024-09-07 | 1 | 39243425 | [
"solid tumors",
"CAR-T cells",
"hematological ones",
"rapid exhaustion",
"cancer",
"CAR-T",
"a hotspot",
"CD122"
] | [
"Astragalus polysaccharide",
"CAR-T",
"CXCR3",
"Hepatocellular carcinoma",
"Memory T cell",
"PD-1"
] | 0 | 10.1016/j.biopha.2024.117401 | [
"Zhang",
"Su",
"Luo",
"Zheng",
"Liang",
"Chen",
"Liu",
"Qiu",
"Liu",
"Feng",
"Dai"
] | [
"Immunology Program, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong 510006, China.",
"Immunology Program, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.",
"Immunology Program, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.",
"Immunology Program, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.",
"Immunology Program, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong 510006, China.",
"Immunology Program, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong 510006, China.",
"Immunology Program, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong 510006, China.",
"Immunology Program, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong 510006, China.",
"Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.",
"Immunology Program, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address: [email protected].",
"Immunology Program, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong 510006, China. Electronic address: [email protected]."
] | [
"39243425"
] | [] | 8.467038 | 4.447227 |
39243423 | 520 | B cells enhance EphA2 chimeric antigen receptor T cells cytotoxicity against glioblastoma via improving persistence. | Chimeric antigen receptor (CAR) T cell therapy is a powerful adoptive immunotherapy against blood cancers, but the therapeutic effect was not efficient enough on solid tumors. B cells have been reported to play a critical role in regulating memory T differentiation and cytotoxic T development. However, as of yet the influence of such B cells on CAR T cells has not been discussed. In this study, using ephrin type-A receptor 2 (EphA2) specific CAR T cells, we cultured B cells successfully to stimulate CAR T cells in vitro, and investigated the cell differentiation and anti-tumor efficiency. We observed that EphA2-CAR T cells stimulated by B cells performed increased interferon γ (IFN γ) production and upregulated OX40 expression, as well as the enhanced anti-tumor activity and reduced PD-1 expression. The persistence of CAR T cells was enhanced after B cells stimulation for more than 7 days with the increased subset of central memory T cells (T | [
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] | 2024-09-07 | 1 | 39243423 | [
"CAR T cells",
"T cell therapy",
"central memory T cells",
"B cells",
"B cells stimulation",
"such B cells",
"memory T differentiation",
"anti-tumor efficiency",
"EphA2-CAR T cells",
"cytotoxic T development",
"Chimeric antigen receptor",
"CAR",
"OX40 expression",
"(EphA2) specific CAR T cells",
"blood cancers",
"the cell differentiation",
"the enhanced anti-tumor activity",
"solid tumors",
"EphA2",
"expression",
"ephrin type-A receptor",
"IFN",
"interferon",
"a powerful adoptive immunotherapy",
"the increased subset",
"the therapeutic effect",
"a critical role",
"(IFN γ) production",
"more than 7 days",
"this study"
] | [
"B cells",
"Chimeric antigen receptor",
"EphA2",
"Glioblastoma"
] | 0 | 10.1016/j.humimm.2024.111093 | [
"Zhang",
"Gu",
"An",
"Huang",
"Zhang",
"Zhong",
"Hu"
] | [
"Beijing Key Laboratory for Therapeutic Cancer Vaccines, Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.",
"Beijing Key Laboratory for Therapeutic Cancer Vaccines, Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.",
"Beijing Key Laboratory for Therapeutic Cancer Vaccines, Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.",
"Beijing Key Laboratory for Therapeutic Cancer Vaccines, Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.",
"Beijing Key Laboratory for Therapeutic Cancer Vaccines, Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.",
"The Clinical Center of Gene and Cell Engineering, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.",
"Beijing Key Laboratory for Therapeutic Cancer Vaccines, Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China. Electronic address: [email protected]."
] | [
"39243423"
] | [] | 8.194202 | 5.436094 |
39242276 | 521 | CD4 | Advances in cancer immunotherapy have transformed cancer care and realized unprecedented responses in many patients. The growing arsenal of novel therapeutics - including immune checkpoint inhibition (ICI), adoptive T cell therapies (ACTs), and cancer vaccines - reflects the success of cancer immunotherapy. The therapeutic benefits of these treatment modalities are generally attributed to the enhanced quantity and quality of antitumor CD8 | [
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] | 2024-09-07 | 279 | 39242276 | [
"cancer immunotherapy",
"cancer care",
"cancer vaccines",
"adoptive T cell therapies",
"immune checkpoint inhibition",
"novel therapeutics",
"unprecedented responses",
"antitumor CD8",
"many patients",
"quality",
"ICI",
"ACTs",
"the enhanced quantity",
"Advances",
"these treatment modalities",
"The therapeutic benefits",
"The growing arsenal",
"the success"
] | [
"CD4(+) T lymphocytes",
"antigen-presenting cells",
"cancer immunotherapy"
] | 0 | 10.1016/j.trecan.2024.07.009 | [
"Montauti",
"Oh",
"Fong"
] | [
"Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.",
"Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.",
"Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA; Immunotherapy Integrated Research Center, Fred Hutchison Cancer Center, Seattle, WA, USA. Electronic address: [email protected]."
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39242251 | 522 | [Prerequisite and organisation of health-care pathways for Cell and Gene therapies, using Mesenchymal Stromal Cells (MSC) or Chimeric Antigen Receptor (CAR) T cells, in patients with autoimmune systemic diseases]. | First-line treatments of autoimmune systemic diseases (ARD) are based on the use of various types of immunosuppressive or immunomodulatory drugs, either alone or in association, according to standardized reference protocols. Prolonged use of these drugs in severe or refractory ARD is associated with high morbidity and increased mortality. Innovative cell therapies represent a new promising approach for patients with ARDs, with the recent clinical use of: a) mesenchymal stromal cells (MSCs), based on their immunomodulatory, antifibrotic and pro-angiogenic properties and b) Chimeric Antigen Receptors (CAR) T cell therapies T lymphocytes, where genetically modified expression of a chimeric antigen receptor (CAR-T cells). Therapeutic use of MSC or CAR-T cells, remains indications of exception in patients with severe ARDs resistant to prior standard therapies with new prerequisite and organisation of health-care pathways as compared to traditional drugs, not only for the Cell and Gene Therapy (CGT) product definition and delivery process, but also for the patient clinical management before and after administration of the CGT product. The aim of this workshop under the auspices of the French Speaking Society of Bone Marrow and Cell transplantation (SFGM-TC) working group on autoimmune diseases (MATHEC) is to describe: a) the prerequisite for French hospitals to set-up the specific health-care pathways for MSC or CART therapy in ARDs patients, in accordance with regulatory and safety needs to perform academic or industry sponsored clinical trials, and b) the care-pathway for ARD patients treated with CGT, highlighting the importance of working in tandem between the ARD and the CAR-T cell specialist all along the indication, procedures and follow-up of ARDs. Patient safety considerations are central to guidance on patient selection to be validated collectively at the multidisciplinary team meeting (MDTM) based on recent (less than 3 months) thorough patient evaluation. MSC and CAR-T procedural aspects and follow-up are then carried out within appropriately experienced and SFGM-TC accredited centres in close collaboration with the ADs specialist. | [
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] | 2024-09-07 | 1 | 39242251 | [
"ARD patients",
"Innovative cell therapies",
"ARDs patients",
"severe ARDs",
"Patient safety considerations",
"autoimmune systemic diseases",
"patient selection",
"sponsored clinical trials",
"ARD",
"autoimmune diseases",
"thorough patient evaluation",
"prior standard therapies",
"traditional drugs",
"new prerequisite",
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"T lymphocytes",
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"standardized reference protocols",
"Bone Marrow",
"high morbidity",
"close collaboration",
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"the recent clinical use",
"French hospitals"
] | [
"Cellules stromales mésenchymateuses",
"Lymphocytes T génétiquement modifiés pour exprimer un récepteur chimérique à l’antigène",
"Lymphocytes genetically modified to express a chimeric antigen receptor",
"Maladies auto-immunes systémiques",
"Mesenchymal stromal cells",
"Systemic autoimmune rheumatological diseases"
] | 0 | 10.1016/j.bulcan.2024.06.008 | [
"Castilla-Llorente",
"Bonnin",
"Lansiaux",
"Tudesq",
"Beuvon",
"Fabreguettes",
"Pers",
"Pugnet",
"Maria",
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"Madelaine",
"Thieblemont",
"Tarte",
"Yakoub-Agha",
"Magro",
"Farge",
"Marjanovic"
] | [
"Département d'hématologie, Gustave-Roussy Cancer Campus, 114, rue Edouard-Vaillant, 94805 Villejuif, France.",
"Service d'hématologie clinique et thérapie cellulaire, hôpital Saint-Antoine, AP-HP, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France.",
"Unité de médecine interne (UF04) : CRMR MATHEC, maladies auto-immunes et thérapie cellulaire, Centre de référence des maladies auto-immunes systémiques rares d'Île-de-France, AP-HP, hôpital St-Louis, 75010 Paris, France; URP3518, IRSL, recherche clinique en hématologie, immunologie et transplantation, université Paris Cité, 75010 Paris, France.",
"Service d'hématologie clinique, CHU de Montpellier, université de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier, France.",
"Service de médecine interne et maladies infectieuses, CHU de Poitiers, 2, rue de la Milétrie, 86000 Poitiers, France.",
"Agence générale des équipements et produits de santé (AGEPS), Assistance publique-Hôpitaux de Paris (AP-HP), 75005 Paris, France.",
"Inserm UMR 1183, Institute for Regenerative Medicine and Biotherapy, University of Montpellier, 34298 Montpellier, France; Inserm, Clinical immunology and osteoarticular diseases Therapeutic Unit, Lapeyronie University Hospital, CHU Montpellier, IRMB, University of Montpellier, Montpellier, France.",
"Service de médecine interne et immunologie clinique, CHU de Toulouse Rangueil, 2, rue Viguerie, 31059 Toulouse, France.",
"Médecine interne et immuno-oncologie (MedI20), CHU de Montpellier, hôpital Saint-Eloi, université de Montpellier, Institute for Regenerative Medicine and Biotherapy (IRMB), 80, avenue Augustin-Fliche, 34295 Montpellier, France.",
"Service de médecine interne et maladies infectieuses, CIC-1402, CHU de Poitiers, 2, rue de la Milétrie, 86000 Poitiers, France; Université de Poitiers, 9, rue de la Milétrie, 86000 Poitiers, France.",
"Service de médecine interne 2, Sorbonne Université, Assistance publique-Hôpitaux de Paris (AP-HP), groupement hospitalier Pitié-Salpêtrière, Centre de référence pour le lupus, le syndrome des anti-phospholipides et autres maladies auto-immunes rares, Paris, France.",
"Département de médecine interne et immunologie clinique, CHU de Lille, 59000 Lille, France; Centre de référence des maladies auto-immunes et auto-inflammatoires rares (CERAINO), 59000 Lille, France.",
"Service d'immunologie clinique et médecine interne, centre de références des maladies auto-immunes et systémiques rares (CNR RESO), hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg, France.",
"Service de dermatologie, hôpital Saint-Louis, Assistance publique-Hôpitaux de Paris, université Paris Cité, Paris, France.",
"Unité de médecine interne (UF04) : CRMR MATHEC, maladies auto-immunes et thérapie cellulaire, Centre de référence des maladies auto-immunes systémiques rares d'Île-de-France, AP-HP, hôpital St-Louis, 75010 Paris, France; URP3518, IRSL, recherche clinique en hématologie, immunologie et transplantation, université Paris Cité, 75010 Paris, France.",
"Department of Internal Medicine & Clinical Immunology, Rennes University Hospital, 35000 Rennes, France.",
"Hematology and transplantation unit, Saint-Louis Hospital, AP-HP, Paris, France.",
"Unité de médecine interne (UF04) : CRMR MATHEC, maladies auto-immunes et thérapie cellulaire, Centre de référence des maladies auto-immunes systémiques rares d'Île-de-France, AP-HP, hôpital St-Louis, 75010 Paris, France; URP3518, IRSL, recherche clinique en hématologie, immunologie et transplantation, université Paris Cité, 75010 Paris, France.",
"Pharmacie, hôpital Saint-Louis, AP-HP, Paris, France; Société française de pharmacie oncologique (SFPO), Paris, France.",
"Hémato-oncologie, DMU DHI, hôpital Saint-Louis, AP-HP, 75010 Paris, France.",
"Équipe labellisée Ligue, UMR_ S 1236, Inserm, Université de Rennes, EFS Bretagne, Rennes, France.",
"Inserm U995, CHU de Lille, LIRIC, université de Lille, 59000 Lille, France.",
"Unité d'allogreffe, maladies du sang, CHRU, 59000 Lille, France.",
"Service d'hématologie clinique et thérapie cellulaire, hôpital Saint-Antoine, AP-HP, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; URP3518, IRSL, recherche clinique en hématologie, immunologie et transplantation, université Paris Cité, 75010 Paris, France; Department of Medicine, McGill University, H3A 1A1 Montreal, Canada.",
"Service d'hématologie clinique et thérapie cellulaire, hôpital Saint-Antoine, AP-HP, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France. Electronic address: [email protected]."
] | [
"39242251"
] | [] | 7.450566 | 4.276571 |
39241743 | 523 | Off-the-shelf CAR-T cells could prove paradigm shifting for autoimmune diseases. | Early reports suggest that chimeric antigen receptor (CAR)-T therapy has remarkable potential for treating autoimmune disease. Current approaches rely on autologous CAR-T cells, creating a bottleneck to the broad deployment of this therapy. In this issue of Cell, Wang et al. | [
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] | 2024-09-07 | 1 | 39241743 | [
"CAR)-T therapy",
"remarkable potential",
"Wang et",
"Current approaches",
"Early reports",
"autoimmune disease",
"autologous CAR-T cells",
"Cell",
"CAR)-T",
"al",
"Wang et al",
"the broad deployment",
"this therapy",
"a bottleneck",
"this issue"
] | [] | 0 | 10.1016/j.cell.2024.07.056 | [
"Baker",
"June"
] | [
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA 19104, USA; Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA. Electronic address: [email protected].",
"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected]."
] | [
"39241743"
] | [] | 7.602929 | 4.244753 |
39241199 | 524 | Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphoma. | Engineered cellular therapy with CD19-targeting chimeric antigen receptor T cells (CAR-Ts) has revolutionized outcomes for patients with relapsed/refractory large B-cell lymphoma (LBCL), but the cellular and molecular features associated with response remain largely unresolved. We analyzed serial peripheral blood samples ranging from the day of apheresis (day -28/baseline) to 28 days after CAR-T infusion from 50 patients with LBCL treated with axicabtagene ciloleucel by integrating single-cell RNA and T-cell receptor sequencing, flow cytometry, and mass cytometry to characterize features associated with response to CAR-T. Pretreatment patient characteristics associated with response included the presence of B cells and increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC). Infusion products from responders were enriched for clonally expanded, highly activated CD8+ T cells. We expanded these observations to 99 patients from the ZUMA-1 cohort and identified a subset of patients with elevated baseline B cells, 80% of whom were complete responders. We integrated B-cell proportion ≥0.5% and ALC/AMC ≥1.2 into a 2-factor predictive model and applied this model to the ZUMA-1 cohort. Estimated progression-free survival at 1 year in patients meeting 1 or both criteria was 65% vs 31% for patients meeting neither criterion. Our results suggest that patients' immunologic state at baseline affects the likelihood of response to CAR-T through both modulation of the T-cell apheresis product composition and promoting a more favorable circulating immune compartment before therapy. These baseline immunologic features, measured readily in the clinical setting before CAR-T, can be applied to predict response to therapy. | [
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] | 2024-09-06 | 1 | 39241199 | [
"B cells",
"elevated baseline B cells",
"patients",
"response",
"CD19-targeting chimeric antigen receptor T cells",
"Engineered cellular therapy",
"increased absolute lymphocyte count",
"serial peripheral blood samples",
"CAR-T. Pretreatment patient characteristics",
"T-cell receptor",
"Infusion products",
"features",
"baseline",
"%",
"flow cytometry",
"patients immunologic state",
"mass cytometry",
"single-cell RNA",
"B-cell proportion",
"the T-cell apheresis product composition",
"relapsed/refractory large B-cell lymphoma",
"therapy",
"axicabtagene ciloleucel",
"LBCL",
"complete responders",
"apheresis",
"ALC",
"CAR-T infusion",
"clonally expanded, highly activated CD8+ T cells",
"day -28/baseline"
] | [] | 0 | 10.1182/blood.2024024381 | [
"Maurer",
"Grabski",
"Houot",
"Gohil",
"Miura",
"Redd",
"Lyu",
"Lu",
"Arihara",
"Budka",
"McDonough",
"Ansuinelli",
"Reynolds",
"Jacene",
"Li",
"Livak",
"Ritz",
"Miles",
"Mattie",
"Neuberg",
"Irizarry",
"Armand",
"Wu",
"Jacobson"
] | [
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nHarvard Medical School, Boston, MA.\nBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.",
"Department of Biostatistics, Harvard University, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nDepartment of Hematology, University Hospital of Rennes, UMR U1236, INSERM, University of Rennes, Rennes, France.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nDepartment of Haematology, University College London, London, United Kingdom.\nDepartment of Haematology, University College London Hospitals National Health Service Foundation Trust, London, United Kingdom.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.",
"Department of Biostatistics, Harvard University, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nTranslational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nTranslational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.",
"Kite, a Gilead Company, Santa Monica, CA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.",
"Harvard Medical School, Boston, MA.\nDepartment of Imaging, Dana-Farber Cancer Institute, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.\nTranslational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nTranslational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nHarvard Medical School, Boston, MA.",
"Kite, a Gilead Company, Santa Monica, CA.",
"Kite, a Gilead Company, Santa Monica, CA.",
"Department of Data Science, Dana-Farber Cancer Institute, Boston, MA.",
"Department of Biostatistics, Harvard University, Boston, MA.\nDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nHarvard Medical School, Boston, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nHarvard Medical School, Boston, MA.\nBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.",
"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.\nHarvard Medical School, Boston, MA."
] | [
"39241199"
] | [] | 5.890308 | 5.383671 |
39240694 | 525 | B7-H3-Targeted CAR-Vδ1T Cells Exhibit Potent Broad-Spectrum Activity against Solid Tumors. | Vδ1T cells, a rare subset of γδT cells, hold promise for treating solid tumors. Unlike conventional T cells, they recognize tumor antigens independently of the MHC antigen presentation pathway, making them a potential "off-the-shelf" cell therapy product. However, isolation and activation of Vδ1T cells is challenging, which has limited their clinical investigation. Here, we developed a large-scale clinical-grade manufacturing process for Vδ1T cells and validated the therapeutic potential of B7-H3 chimeric antigen receptor (CAR)-modified Vδ1T cells in treating solid tumors. Coexpression of IL2 with the B7-H3-CAR led to durable antitumor activity of Vδ1T cells in vitro and in vivo. In multiple subcutaneous and orthotopic mouse xenograft tumor models, a single intravenous administration of the CAR-Vδ1T cells resulted in complete tumor regression. These modified cells demonstrated significant in vivo expansion and robust homing ability to tumors, akin to natural tissue-resident immune cells. Additionally, the B7-H3-CAR-Vδ1T cells exhibited a favorable safety profile. In conclusion, B7-H3-CAR-modified Vδ1T cells represent a promising strategy for treating solid tumors. Significance: A clinical-grade expansion protocol enabled generation of B7-H3-targeted CAR-Vδ1T cells with robust anticancer activity and a favorable safety profile, supporting the potential of CAR-Vδ1T cells as an "off-the-shelf" therapy for solid tumors. | [
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] | 2024-09-06 | 42 | 39240694 | [
"Vδ1T cells",
"CAR)-modified Vδ1T cells",
"conventional T cells",
"γδT cells",
"CAR-Vδ1T cells",
"-Vδ1T cells",
"tumor antigens",
"solid tumors",
"tumors",
"complete tumor regression",
"B7-H3-targeted CAR-Vδ1T cells",
"B7-H3-CAR-modified Vδ1T cells",
"natural tissue-resident immune cells",
"robust anticancer activity",
"robust homing ability",
"B7-H3 chimeric antigen receptor",
"vivo expansion",
"the B7-H3-CAR-Vδ1T cells",
"multiple subcutaneous and orthotopic mouse xenograft tumor models",
"These modified cells",
"durable antitumor activity",
"B7-H3",
"B7-H3-CAR",
"a favorable safety profile",
"B7-H3-targeted",
"A clinical-grade expansion protocol",
"the MHC antigen presentation",
"generation",
"promise",
"MHC"
] | [] | 0 | 10.1158/0008-5472.CAN-24-0195 | [
"Jiang",
"You",
"Wu",
"Qi",
"Xiang",
"Zhang",
"Meng",
"Wang",
"Huang",
"Li",
"Chen",
"An",
"Yang",
"Zhang",
"Shen",
"Yang"
] | [
"Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China.",
"PersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China.",
"Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China.",
"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China.",
"PersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China.",
"PersonGen.Anke Cellular Therapeutics Co., Ltd., Hefei, China.",
"PersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China.",
"PersonGen.Anke Cellular Therapeutics Co., Ltd., Hefei, China.",
"PersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China.",
"PersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China.",
"PersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China.",
"Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China.",
"PersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China.",
"PersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China.\nPersonGen.Anke Cellular Therapeutics Co., Ltd., Hefei, China.",
"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China.",
"Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China.\nPersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China.\nPersonGen.Anke Cellular Therapeutics Co., Ltd., Hefei, China."
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] | [] | 9.607909 | 4.816992 |
39240498 | 526 | Investigating the Influence of Covariates on Axicabtagene Ciloleucel (axi-cel) Kinetics in Patients with Non-Hodgkin's Lymphoma. | Axicabtagene ciloleucel (axi-cel, Yescarta) is an autologous, anti-CD19, chimeric antigen receptor (CAR) T-cell therapy approved for patients with relapsed and refractory non-Hodgkin's lymphoma. Substantial inter-individual variability in cellular kinetics has been observed with CAR-T therapies and factors impacting CAR-T cellular kinetics remain poorly understood. This work reports a population cellular kinetic model of axi-cel in relapsed and patients with refractory non-Hodgkin's lymphoma and investigated the impact of covariates on early and late kinetic phases of CAR-T exposure.
A population cellular kinetic model (NONMEM
Axi-cel cellular kinetics were well described by a piecewise model of cellular growth kinetics characterized by an exponential growth phase followed by a triphasic decline phase including a long-term persistence phase. The final cellular kinetic model retained in vitro doubling time during CAR-T cell manufacturing and total number of T cells infused as covariates impacting the duration of the growth phase, which, however, did not substantially influence maximum concentration, area under the concentration-time curve over the first 28 days, or long-term persistence. A statistically significant relationship was observed between maximum concentration and the probability to receive tocilizumab and/or corticosteroids.
No covariates considered in this study were found to significantly and substantially predict the exposure profile of axi-cel. Tocilizumab and steroid use were related to maximum concentration, but they were used reactively to treat toxicities that are associated with a higher maximum concentration. Further CAR-T kinetic analyses should consider additional factors to explain the observed variability in cellular kinetics or help establish a dose-exposure relationship.
NCT02348216 (ZUMA-1), NCT03105336 (ZUMA-5), and NCT03391466 (ZUMA-7). | [
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10.1016/S0140-6736(20)31366-0 | [
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"Certara North America, Certara Canada, 2000 Peel Street, Suite 570 Montréal, Québec H3A 2W5, Radnor, PA, USA. [email protected].",
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"Certara North America, Certara Canada, 2000 Peel Street, Suite 570 Montréal, Québec H3A 2W5, Radnor, PA, USA.",
"Gilead Sciences, Parsipanny, NJ, USA.",
"Kite, A Gilead Company, Santa Monica, CA, USA.",
"Kite, A Gilead Company, Santa Monica, CA, USA.",
"Certara North America, Certara Canada, 2000 Peel Street, Suite 570 Montréal, Québec H3A 2W5, Radnor, PA, USA.",
"Kite, A Gilead Company, Santa Monica, CA, USA.",
"Kite, A Gilead Company, Santa Monica, CA, USA.",
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"Certara North America, Certara Canada, 2000 Peel Street, Suite 570 Montréal, Québec H3A 2W5, Radnor, PA, USA.",
"Certara North America, Certara Canada, 2000 Peel Street, Suite 570 Montréal, Québec H3A 2W5, Radnor, PA, USA.",
"Kite, A Gilead Company, Santa Monica, CA, USA. [email protected]."
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39240078 | 527 | Therapeutic Efficacy of IL7/CCL19-Expressing CAR-T Cells in Intractable Solid Tumor Models of Glioblastoma and Pancreatic Cancer. | Cancer immunotherapy using immune checkpoint inhibitors and its combination with other anticancer therapies has emerged as a new standard of care because of the encouraging therapeutic effects in various solid cancers. Nonetheless, glioblastoma and pancreatic cancer remain resistant to immunotherapy and represent intractable cancers with the poorest prognosis. We investigated the therapeutic effects of next-generation chimeric antigen receptor (CAR) T cells producing IL7 and chemokine (C-C motif) ligand 19 (CCL19; referred to as 7 × 19 CAR-T) in these intractable cancers. Cytotoxic activities and therapeutic effects of 7 × 19 CAR-T were evaluated in vitro and in vivo, in a model using EGFR variant III (EGFRvIII)-positive glioblastoma and anti-EGFRvIII CAR-T generated from healthy donor peripheral blood mononuclear cells (PBMC), or a model using HER2-positive pancreatic cancer organoids and anti-HER2 CAR-T generated from the same patient's PBMC. Anti-EGFRvIII 7 × 19 CAR-T exhibited cytotoxic activity specific to EGFRvIII-positive tumor, induced complete rejection of glioblastoma with massive T-cell infiltration and tumor cell death in the tumor tissues, and consequently prolonged mouse survival. Anti-HER2 7 × 19 CAR-T demonstrated a potent cytotoxic activity against autologous HER2-positive pancreatic cancer organoids and induced complete rejection of autologous tumor along with prolonged mouse survival. Our results suggest that 7 × 19 CAR-T could become a therapeutic option for glioblastoma and pancreatic cancer. To the best of our knowledge, this is the first study to demonstrate the therapeutic efficacy of next-generation CAR-T in an autologous model using patient-derived tumor organoids and CAR-T generated from the same patient's PBMC, in which unwanted allogeneic immune responses are fully excluded.
Despite the clinical development of CAR T-cell therapy, its efficacy in solid cancers has yet to be established. This study explored the therapeutic potential and immunologic mechanisms of IL7/CCL19-producing CAR-T therapy in preclinical solid cancer models of glioblastoma and pancreatic cancer. We found that IL7/CCL19-producing CAR-T cells generated from the patient's PBMC showed potent therapeutic effects against the solid cancer model established by inoculating organoids from the autologous tumor tissue. | [
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] | 2024-09-06 | 37 | 39240078 | [
"preclinical solid cancer models",
"potent therapeutic effects",
"solid cancers",
"therapeutic effects",
"pancreatic cancer",
"various solid cancers",
"tumor cell death",
"intractable cancers",
"Cancer immunotherapy",
"autologous tumor",
"CAR",
"CAR T-cell therapy",
"anti-HER2 CAR-T",
"healthy donor peripheral blood mononuclear cells",
"autologous HER2-positive pancreatic cancer organoids",
"anti-EGFRvIII CAR-T",
"HER2-positive pancreatic cancer organoids",
"other anticancer therapies",
"Cytotoxic activities",
"cytotoxic activity",
"Anti-HER2",
"unwanted allogeneic immune responses",
"inoculating organoids",
"immune checkpoint inhibitors",
"the solid cancer model",
"CAR-T",
"glioblastoma",
"HER2",
"prolonged mouse survival",
"patient-derived tumor organoids"
] | [] | 0 | 10.1158/2767-9764.CRC-24-0226 | [
"Ohta",
"Sakoda",
"Adachi",
"Shinozaki",
"Nakajima",
"Yasuda",
"Nagano",
"Tamada"
] | [
"Department of ImmunologyYamaguchi University Graduate School of Medicine, Ube, Japan.\nDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.",
"Department of ImmunologyYamaguchi University Graduate School of Medicine, Ube, Japan.",
"Department of ImmunologyYamaguchi University Graduate School of Medicine, Ube, Japan.",
"Department of Pulmonary Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo.",
"Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.",
"Department of Pulmonary Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo.",
"Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.",
"Department of ImmunologyYamaguchi University Graduate School of Medicine, Ube, Japan."
] | [
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] | [] | 9.738117 | 6.200312 |
39239742 | 528 | Tetraspanins in digestive‑system cancers: Expression, function and therapeutic potential (Review). | The tetraspanin family of membrane proteins is essential for controlling different biological processes such as cell migration, penetration, adhesion, growth, apoptosis, angiogenesis and metastasis. The present review summarized the current knowledge regarding the expression and roles of tetraspanins in different types of cancer of the digestive system, including gastric, liver, colorectal, pancreatic, esophageal and oral cancer. Depending on the type and context of cancer, tetraspanins can act as either tumor promoters or suppressors. In the present review, the importance of tetraspanins in serving as biomarkers and targets for different types of digestive system‑related cancer was emphasized. Additionally, the molecular mechanisms underlying the involvement of tetraspanins in cancer progression and metastasis were explored. Furthermore, the current challenges are addressed and future research directions for advancing investigations related to tetraspanins in the context of digestive system malignancies are proposed. | [
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] | 2024-09-06 | 214 | 39239742 | [
"digestive system‑related cancer",
"tetraspanins",
"different types",
"cancer progression",
"digestive system malignancies",
"different biological processes",
"cancer",
"future research directions",
"cell migration",
"membrane proteins",
"context",
"The tetraspanin family",
"metastasis",
"adhesion",
"growth",
"penetration",
"the digestive system",
"investigations",
"gastric",
"apoptosis",
"roles",
"biomarkers",
"targets",
"angiogenesis",
"suppressors",
"the current knowledge",
"gastric, liver, colorectal, pancreatic, esophageal and oral cancer",
"The present review",
"the present review",
"the current challenges"
] | [
"5‑FU",
"5‑Fluorouracil; ALCAM",
"B cells and dendritic cells; CAR‑T",
"activated leukocyte cell adhesion molecule; BMDCs",
"cancer‑initiating cells; DCs",
"chimeric antigen receptor T cells; CDDP",
"cisplatin; CDK4",
"cyclin‑dependent kinase 4; CIC",
"dendritic cells; DFS",
"disease‑free survival; EC2",
"epithelial cell adhesion molecule; ESCC",
"epithelial‑mesenchymal transition; EpCAM",
"one large extracellular loop; EMT"
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10.3389/fimmu.2022.998266 | [
"Chen",
"Li",
"Li",
"Jiang",
"Chen",
"Jiang",
"Li",
"Zhang"
] | [
"School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.",
"School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.",
"Department of Medical Imaging, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.",
"School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.",
"Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.",
"Department of General Surgery (Thyroid Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.",
"School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.",
"Department of Cardiology, Institute of Cardiovascular Research, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China."
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39238483 | 529 | Locoregional CAR T Cells for the Treatment of CNS Tumors in Children: Investigational Drug Service Pharmacy Activities. | A major obstacle in translating the therapeutic potential of chimeric antigen receptor (CAR) T cells to children with central nervous system (CNS) tumors is the blood-brain barrier. To overcome this limitation, preclinical and clinical studies have supported the use of repeated, locoregional intracranial CAR T-cell delivery. However, there is limited literature available describing the process for the involvement of an investigational drug service (IDS) pharmacy, particularly in the setting of a children's hospital with outpatient dosing for CNS tumors.
To describe Seattle Children's Hospital's experience in clinically producing CAR T cells and the implementation of IDS pharmacy practices used to deliver more than 300 intracranial CAR T-cell doses to children, as well as to share how we refined the processing techniques from CAR T-cell generation to the thawing of fractionated doses for intracranial delivery.
Autologous CD4+ and CD8+ T cells were collected and transduced to express HER2, EGFR, or B7-H3-specific CAR T cells. Cryopreserved CAR T cells were thawed by the IDS pharmacy before intracranial delivery to patients with recurrent/refractory CNS tumors or with diffuse intrinsic pontine glioma/diffuse midline glioma.
The use of a thaw-and-dilute procedure for cryopreserved individual CAR T-cell doses provides reliable viability and is more efficient than typical thaw-and-wash protocols. Cell viability with the thaw-and-dilute protocol was approximately 75% and was always within 10% of the viability assessed at cryopreservation. Cell viability was preserved through 6 hours after thawing, which exceeded the 1-hour time frame from thawing to infusion.
As the field of adoptive immunotherapy grows and continues to bring hope to patients with fatal CNS malignancies, it is critical to focus on improving the preparatory steps for CAR T-cell delivery. | [
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] | 2024-09-06 | 12 | 39238483 | [
"CAR T cells",
"Cell viability",
"cryopreserved individual CAR T-cell doses",
"CAR T-cell delivery",
"CNS tumors",
"IDS pharmacy practices",
"CAR T-cell generation",
"intracranial delivery",
"Autologous CD4+ and CD8+ T cells",
"fatal CNS malignancies",
"clinically producing CAR T cells",
"repeated, locoregional intracranial CAR T-cell delivery",
"reliable viability",
"fractionated doses",
"CNS",
"children",
"CAR",
"B7-H3-specific CAR T cells",
"more than 300 intracranial CAR T-cell doses",
"patients",
"limited literature",
"diffuse intrinsic pontine glioma/diffuse midline glioma",
"recurrent/refractory CNS tumors",
"outpatient dosing",
"thawing",
"the IDS pharmacy",
"hope",
"HER2",
"EGFR",
"central nervous system (CNS) tumors"
] | [
"CAR T cells",
"CNS tumors",
"central nervous system",
"cryopreservation",
"immunotherapy",
"investigational drug service pharmacy",
"pediatric brain tumor",
"pediatric cancer",
"pharmacy practices",
"pharmacy protocols"
] | 0 | null | [
"Vitanza",
"Choe",
"Brown",
"Beebe",
"Kong",
"Rogers",
"Jacob",
"Mano",
"Abuan",
"Mgebroff",
"Lindgren",
"Gustafson",
"Wilson",
"Noll",
"Ronsley",
"Crotty",
"Leary",
"Foster",
"Pinto",
"Gust",
"Gardner",
"Park",
"Jensen"
] | [
"University of Washington (UW), a Laboratory Principal Investigator (PI) at the Ben Towne Center for Childhood Cancer Research at Seattle Children's Research Institute (SCRI), and a Neuro-Oncologist at Seattle Children's Hospital (SCH).",
"Fred Hutch Cancer Center and an Assistant Professor of Pediatrics at UW.",
"Good Manufacturing Practice (GMP) Cell Production, SCRI.",
"GMP Cell Production, SCRI.",
"Clinical Research Support Cores, SCH.",
"SCH.",
"SCH.",
"SCH.",
"SCH.",
"GMP Quality Control, SCRI.",
"Therapeutics Cell Manufacturing Facility/Quality Assurance, SCRI.",
"Research and Development, Seattle Children's Therapeutics (SCTx).",
"Therapeutics Correlative Science, SCTx.",
"UW.",
"Pediatrics at UW and a Neuro-Oncologist at SCH.",
"Pediatrics at UW and a Neuro-Oncologist at SCH.",
"Pediatrics at UW and a Neuro-Oncologist at SCH.",
"Children's Hospital of Philadelphia and Pediatric Neuro-Oncologist at the University of Pennsylvania.",
"Pediatrics at UW and an Oncologist at SCH.",
"Pediatrics at UW, a Laboratory PI at the Center for Integrated Brain Health at SCRI, and a Neurologist at SCH.",
"Pediatrics at UW, an Oncologist at SCH, and the Associate Medical Director of SCTx.",
"Pediatrics at UW, an Oncologist at SCH, and the Medical Director of SCTx.",
"Chief Therapeutics Officer of SCTx."
] | [
"39238483",
"28408462",
"31290035",
"27157931",
"32341580",
"26059190",
"28029927",
"34253928",
"36259971",
"31903167",
"8797582",
"27836802"
] | [] | 9.716179 | 7.150311 |
39235920 | 530 | Patterns of metabolic response in patients receiving commercial CAR T-cells for relapsing/refractory aggressive B cells lymphoma. | CAR T-cells is an innovative treatment for relapsed/refractory aggressive B cell lymphomas, initially proposed as third-line therapy and beyond, now allowed as soon as second-line treatment for patients with early relapse after first-line treatment. FDG PET/CT remains the modality of choice to evaluate response to this therapeutic strategy, to detect or confirm treatment failure, and allow for salvage therapy if needed. Correct classification of patients regarding response is thus of the utmost importance. In many cases, metabolic response follows classical known patterns, and Deauville score and Lugano criteria yield accurate characterization of patient status. However, given its specific mode of action, it can result in delayed response or atypical patterns of response. We report here a few examples of response from our experience to illustrate the existence of tricky cases. These atypical cases require multidisciplinary management, with clinical, biological, imaging, and pathological work-up. | [
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] | 2024-09-05 | 1 | 39235920 | [
"delayed response",
"metabolic response",
"response",
"treatment failure",
"classical known patterns",
"atypical patterns",
"tricky cases",
"many cases",
"accurate characterization",
"Lugano criteria",
"multidisciplinary management",
"salvage therapy",
"Deauville score",
"patients",
"relapsed/refractory aggressive B cell lymphomas",
"early relapse",
"first-line treatment",
"second-line treatment",
"patient status",
"imaging",
"action",
"Lugano",
"choice",
"Deauville",
"third-line therapy",
"lymphomas",
"third",
"an innovative treatment",
"first",
"second"
] | [
"CAR T-cells",
"FDG PET",
"lymphoma",
"therapeutic evaluation"
] | 0 | 10.1093/bjr/tqae178 | [
"Vercellino",
"Betterki",
"Blanc",
"de Kerviler",
"Cristinelli",
"Merlet",
"Thieblemont",
"Meignin",
"Di Blasi"
] | [
"Nuclear Medicine Department, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010, Paris, France.\nINSERM UMR_S942, Université Paris Cité, 75006, Paris, France.",
"Nuclear Medicine Department, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010, Paris, France.",
"Nuclear Medicine Department, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010, Paris, France.",
"Radiology Department, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010, Paris, France.",
"Hemato-Oncology Department, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010, Paris, France.",
"Nuclear Medicine Department, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010, Paris, France.",
"Hemato-Oncology Department, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010, Paris, France.",
"Pathology Department, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010, Paris, France.",
"Hemato-Oncology Department, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010, Paris, France."
] | [
"39235920"
] | [] | 6.699217 | 5.309474 |
39235633 | 531 | Correction to: Impact of fludarabine and treosulfan on ovarian tumor cells and mesothelin chimeric antigen receptor T cells. | null | [
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] | 2024-09-05 | 1 | 39235633 | [] | [] | 0 | 10.1007/s00262-024-03813-3 | [
"El-Seraf",
"Nilsson",
"Moter",
"Duan",
"Mattsson",
"Magalhaes"
] | [
"Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. [email protected].\nBasic Medical Sciences Department, College of Medicine, Ajman University, Ajman, UAE. [email protected].",
"Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.",
"Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.",
"Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.",
"Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.\nGloria and Seymour Epstein Chair in Cell Therapy and Transplantation, Princess Margaret Cancer Centre and University of Toronto, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.",
"Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.\nDepartment of Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden."
] | [
"39235633"
] | [] | 32.992279 | 7.525297 |
39234101 | 532 | CAR-T therapy pulmonary adverse event profile: a pharmacovigilance study based on FAERS database (2017-2023). | Chimeric antigen receptor T-cell (CAR-T) therapy, a rapidly emerging treatment for cancer that has gained momentum since its approval by the FDA in 2017, involves the genetic engineering of patients' T cells to target tumors. Although significant therapeutic benefits have been observed, life-threatening adverse pulmonary events have been reported.
Using SAS 9.4 with MedDRA 26.1, we retrospectively analyzed data from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database, covering the period from 2017 to 2023. The analysis included the Reporting Odds Ratio Proportional Reporting Ratio Information Component and Empirical Bayes Geometric Mean to assess the association between CAR-T cell therapy and adverse pulmonary events (PAEs).
The FAERS database recorded 9,400 adverse events (AEs) pertaining to CAR-T therapies, of which 940 (10%) were PAEs. Among these CAR-T cell-related AEs, hypoxia was the most frequently reported (344 cases), followed by respiratory failure (127 cases). Notably, different CAR-T cell treatments demonstrated varying degrees of association with PAEs. Specifically, Tisa-cel was associated with severe events including respiratory failure and hypoxia, whereas Axi-cel was strongly correlated with both hypoxia and tachypnea. Additionally, other CAR-T therapies, namely, Brexu-cel, Liso-cel, Ide-cel, and Cilta-cel, have also been linked to distinct PAEs. Notably, the majority of these PAEs occurred within the first 30 days post-treatment. The fatality rates varied among the different CAR-T therapies, with Tisa-cel exhibiting the highest fatality rate (43.6%), followed by Ide-cel (18.8%).
This study comprehensively analyzed the PAEs reported in the FAERS database among recipients of CAR-T cell therapy, revealing conditions such as hypoxia, respiratory failure, pleural effusion, and atelectasis. These CAR-T cell therapy-associated events are clinically significant and merit the attention of clinicians and researchers. | [
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"adverse pulmonary events",
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] | [
"CAR T cell therapy",
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"chimeric antigen receptor T cells",
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"pulmonary adverse events",
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] | 0 | 10.3389/fphar.2024.1434231
10.1016/S0140-6736(20)31366-0
10.1016/j.jacc.2019.10.038
10.1172/jci.insight.136012
10.3389/fimmu.2022.1079181
10.1016/j.psychres.2023.115300
10.1007/s11899-023-00687-7
10.1161/CIRCULATIONAHA.120.048100
10.1016/j.ymthe.2023.06.006
10.1016/S1470-2045(21)00591-X
10.1016/S2352-3026(21)00369-0
10.1016/j.cell.2022.03.041
10.1016/j.bbmt.2018.12.758
10.1016/j.jaccao.2020.04.012
10.1182/blood.2021011898
10.1200/JCO.22.00842
10.1056/NEJMoa1709866
10.1007/s40261-017-0503-6
10.1056/NEJMoa2024850
10.2147/ITT.S202015
10.1038/nrclinonc.2017.148
10.1056/NEJMoa1709919
10.1056/NEJMoa1804980
10.1136/jitc-2020-001159
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10.1016/j.ccell.2019.02.003
10.1038/s41408-021-00459-7
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10.3389/fphar.2022.851246
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10.1200/JCO.22.01797
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10.1016/j.jaip.2020.09.021 | [
"Shi",
"Liu",
"Jiang",
"Gao",
"Yu",
"Zhang",
"Wu"
] | [
"Xinjiang Medical University, Urumqi, China.\nDepartment of Oncology Cardiology, Xinjiang Medical University Cancer Hospital, Urumqi, China.",
"Xinjiang Medical University, Urumqi, China.\nThe Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, China.",
"Department of Oncology Cardiology, Xinjiang Medical University Cancer Hospital, Urumqi, China.",
"Department of Oncology Cardiology, Xinjiang Medical University Cancer Hospital, Urumqi, China.",
"Department of Oncology Cardiology, Xinjiang Medical University Cancer Hospital, Urumqi, China.",
"Xinjiang Medical University, Urumqi, China.",
"Department of Oncology Cardiology, Xinjiang Medical University Cancer Hospital, Urumqi, China."
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39231778 | 533 | [The impact of immune cells selection on the therapeutic efficacy of CAR-T cell therapy]. | Here we summarized novel Chimeric antigen receptor T-cell immunotherapy (CAR-T) based on the immune material aspect. Young healthy donor T cells, stem cell-like memory T cells, human induced pluripotent stem cells and umbilical cord blood T cells are all potential candidates to enhance CAR-T cell therapy depending on their anti-tumor efficacy. Besides, due to less restricted major histocompatibility complex (MHC) mismatch effect, viral specific T cells, γδT cells, invariant natural killer T cells and macrophages also become idealized T cell sources in terms of Universal CAR-T (UCAR-T) cell therapeutics. In addition, studies demonstrated that more balanced CD4(+)/CD8(+) T cell ratio and eliminating monocytes during leukapheresis have a positive influence on CAR-T cell functioning, whereas T cells with higher exhaustion markers expression hampers anti-tumor ability of CAR-T cells after infusion. To avoid application of such T cells or mitigate the impact using immune checkpoint inhibitors is of great importance.
从免疫细胞层面总结了各种新型嵌合抗原受体T细胞（CAR-T细胞）疗法，健康年轻受试者的T细胞、干性记忆样T细胞、人体诱导多能干细胞、脐带血T细胞来源的CAR-T细胞疗法可增强肿瘤杀伤效应。从通用型CAR细胞方面，病毒特异性T细胞、γδT细胞、iNKT细胞、巨噬细胞等能有效减轻移植物抗宿主病反应。此外，增强去白细胞过程中单核细胞的清除、保持CD4(+)/CD8(+) T细胞均衡比例等策略也是增强CAR-T细胞扩增及杀伤效力的方法。细胞耗竭标志物高表达的T细胞对CAR-T细胞的转导、扩增及发挥杀伤效力等会产生负向影响，使用免疫检查点阻断剂等方式抑制T细胞耗竭能提高CAR-T细胞作用效应。. | [
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"such T cells",
"viral specific T cells",
"idealized T cell sources",
"invariant natural killer T cells",
"Young healthy donor T cells",
"umbilical cord blood T cells",
"human induced pluripotent stem cells",
"stem cell-like memory T cells",
"CAR-T cell functioning",
"CAR-T cell therapy",
"CAR-T cells",
"novel Chimeric antigen receptor T-cell immunotherapy",
"anti-tumor ability",
"immune checkpoint inhibitors",
"more balanced CD4(+)/CD8(+) T cell ratio",
"higher exhaustion markers expression",
"γδT cells",
"potential candidates",
"their anti-tumor efficacy",
"great importance",
"CAR-T",
"MHC",
"leukapheresis",
"monocytes",
"Chimeric",
"terms",
"UCAR-T",
"T细胞作用效应",
"macrophages",
"the immune material aspect"
] | [] | 0 | 10.3760/cma.j.cn121090-20240321-00104
10.3389/fimmu.2021.744823
10.1038/s41375-021-01324-z
10.3389/fimmu.2023.1270843
10.1038/nm.2446
10.1016/j.clim.2022.109078
10.1038/leu.2015.247
10.1038/s41392-023-01659-2
10.1182/blood.2020005278
10.1038/s41591-018-0010-1
10.1126/scitranslmed.abh0272
10.1038/s41577-019-0223-7
10.1182/blood-2013-06-506741
10.3389/fimmu.2020.618427
10.1038/s41573-019-0051-2
10.1038/s41551-022-00969-0
10.1016/j.stem.2022.02.009
10.1080/17474086.2018.1431119
10.1182/blood-2003-05-1732
10.1007/s12026-022-09340-6
10.3389/fonc.2022.944248
10.1016/j.jcyt.2022.05.003
10.3389/fped.2023.1232281
10.1172/JCI85309
10.1126/scitranslmed.3010162
10.1038/s41598-021-92808-6
10.1038/nri3369
10.1016/j.ccell.2018.08.017
10.1155/2022/2112898
10.3389/fimmu.2020.01347
10.1002/cti2.1373
10.1038/s41587-020-0462-y
10.1016/j.biopha.2021.111605 | [
"Qi",
"Zhang",
"Jing"
] | [
"Department of Hematology, Peking University Third Hospital, Beijing 100191, China.",
"Department of Hematology, Peking University Third Hospital, Beijing 100191, China.",
"Department of Hematology, Peking University Third Hospital, Beijing 100191, China."
] | [
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] | [] | 9.500467 | 4.942633 |
39231214 | 534 | TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation. | Low antigen sensitivity and a gradual loss of effector functions limit the clinical applicability of chimeric antigen receptor (CAR)-modified T cells and call for alternative antigen receptor designs for effective T cell-based cancer immunotherapy. Here, we applied advanced microscopy to demonstrate that TCR/CD3-based synthetic constructs (TCC) outperform second-generation CAR formats with regard to conveyed antigen sensitivities by up to a thousandfold. TCC-based antigen recognition occurred without adverse nonspecific signaling, which is typically observed in CAR-T cells, and did not depend-unlike sensitized peptide/MHC detection by conventional T cells-on CD4 or CD8 coreceptor engagement. TCC-endowed signaling properties may prove critical when targeting antigens in low abundance and aiming for a durable anticancer response. | [
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"Low antigen sensitivity",
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"conveyed antigen sensitivities",
"conventional T cells",
"antigens",
"effective T cell-based cancer immunotherapy",
"adverse nonspecific signaling",
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"TCC-endowed signaling properties",
"CD4 or CD8 coreceptor engagement",
"a durable anticancer response",
"a gradual loss",
"the clinical applicability",
"a thousandfold",
"we",
"which"
] | [] | 0 | 10.1126/sciadv.adj4632 | [
"Mühlgrabner",
"Peters",
"Velasco Cárdenas",
"Salzer",
"Göhring",
"Plach",
"Höhrhan",
"Perez",
"Goncalves",
"Farfán",
"Lehner",
"Stockinger",
"Schamel",
"Schober",
"Busch",
"Hudecek",
"Dushek",
"Minguet",
"Platzer",
"Huppa"
] | [
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.",
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.",
"Department of Immunology, Faculty of Biology, University of Freiburg, Germany.\nCenter for Biological Signaling Studies (BIOSS), University of Freiburg, Germany.\nCenter for Integrative Biological Signaling Studies (CIBSS), University of Freiburg, Germany.",
"St. Anna Children's Cancer Research Institute (CCRI), 1090, Vienna, Austria.\nChristian Doppler Laboratory for Next Generation CAR T Cells, 1090, Vienna, Austria.",
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.",
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.",
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.",
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.",
"Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, UK.",
"St. Anna Children's Cancer Research Institute (CCRI), 1090, Vienna, Austria.\nChristian Doppler Laboratory for Next Generation CAR T Cells, 1090, Vienna, Austria.",
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.",
"Department of Immunology, Faculty of Biology, University of Freiburg, Germany.\nCenter for Biological Signaling Studies (BIOSS), University of Freiburg, Germany.\nCenter for Integrative Biological Signaling Studies (CIBSS), University of Freiburg, Germany.",
"Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.",
"Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.",
"Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.",
"Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, UK.",
"Department of Immunology, Faculty of Biology, University of Freiburg, Germany.\nCenter for Biological Signaling Studies (BIOSS), University of Freiburg, Germany.\nCenter for Integrative Biological Signaling Studies (CIBSS), University of Freiburg, Germany.",
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.",
"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria."
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39230837 | 535 | Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma. | The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy. | [
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] | [
"Chimeric antigen receptor T cell",
"Multiple myeloma",
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] | 0 | 10.1007/s10238-024-01477-y | [
"Ma",
"Zhang",
"Liu",
"Li",
"Chen",
"Zhang",
"Qiao",
"Qi",
"Shen",
"Sun",
"Song",
"Cao",
"Cheng",
"Zhu",
"Yan",
"Sang",
"Li",
"Sun",
"Zheng",
"Li",
"Xu",
"Chen"
] | [
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nDepartment of Hematology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, 200434, Shanghai, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Health Screening Center, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.\nCenter of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China. [email protected].\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China. [email protected].\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].",
"Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China. [email protected].\nBlood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].\nThe Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, Jiangsu, China. [email protected]."
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39228124 | 536 | Intrinsic ADRB2 inhibition improves CAR-T cell therapy efficacy against prostate cancer. | Chimeric antigen receptor (CAR)-T cell therapy has shown limited success in patients with solid tumors. Recent in vitro and in vivo data have shown that adrenoceptor beta-2 (ADRB2) is a novel checkpoint receptor that inhibits T cell-mediated anti-tumor responses. To inhibit ADRB2-mediated inhibitory signaling, we downregulated ADRB2 in CAR-T (shβ | [
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] | 2024-09-04 | 52 | 39228124 | [
"CAR)-T cell therapy",
"Chimeric antigen receptor",
"ADRB2",
"limited success",
"vivo data",
"solid tumors",
"T cell-mediated anti-tumor responses",
"CAR)-T",
"patients",
"a novel checkpoint receptor",
"(ADRB2",
"CAR-T",
"that adrenoceptor",
"(shβ",
"that",
"we"
] | [
"ADRB2",
"CAR",
"CAR-T cell therapy",
"adrenergic stress",
"adrenoceptor beta-2",
"chimeric antigen receptor",
"combination therapy",
"immune checkpoint",
"immunotherapy",
"neuroimmunology",
"prostate cancer",
"tumor microenvironment"
] | 0 | 10.1016/j.ymthe.2024.08.028 | [
"Ajmal",
"Farooq",
"Duan",
"Yao",
"Gao",
"Hui",
"Ge",
"Chen",
"Ren",
"Du",
"Jiang"
] | [
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.",
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.",
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.",
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.",
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China; Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.",
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.",
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.",
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.",
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China; College of Life Science, Xinjiang Normal University, Urumqi 830053, China.",
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.",
"Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: [email protected]."
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39227445 | 537 | Fratricide-resistant CD7-CAR T cells in T-ALL. | T cell acute lymphoblastic leukemia (T-ALL) is difficult to treat when it relapses after therapy or is chemoresistant; the prognosis of patients with relapsed or refractory T-ALL is generally poor. We report a case series of 17 such patients who received autologous chimeric antigen receptor (CAR) T cells expressing an anti-CD7 CAR and an anti-CD7 protein expression blocker (PEBL), which prevented CAR T cell fratricide. Despite high leukemic burden and low CAR T cell dosing, 16 of the 17 patients attained minimal residual disease-negative complete remission within 1 month. The remaining patient had CD7 | [
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"Viva-University Children's Cancer Center, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore.\nDepartment of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.",
"Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.",
"Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.",
"National University Cancer Institute, National University Hospital, National University Health System, Singapore, Singapore.",
"National University Cancer Institute, National University Hospital, National University Health System, Singapore, Singapore.",
"Viva-University Children's Cancer Center, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore.\nDepartment of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.",
"Viva-University Children's Cancer Center, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore.\nDepartment of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.",
"National University Cancer Institute, National University Hospital, National University Health System, Singapore, Singapore.",
"Division of Infectious Diseases, Department of Medicine, National University Health System, Singapore, Singapore.",
"Emerging Infectious Diseases Programme, Duke-NUS Medical School, Singapore, Singapore.",
"Emerging Infectious Diseases Programme, Duke-NUS Medical School, Singapore, Singapore.",
"Emerging Infectious Diseases Programme, Duke-NUS Medical School, Singapore, Singapore.",
"Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.",
"Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.",
"Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.",
"Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. [email protected].\nDepartment of Life Sciences and Public Health, Catholic University of the Sacred Heart, Rome, Italy. [email protected].",
"Viva-University Children's Cancer Center, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore. [email protected].\nDepartment of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. [email protected].\nNational University Cancer Institute, National University Hospital, National University Health System, Singapore, Singapore. [email protected].\nCancer Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. [email protected].",
"Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.\nNational University Cancer Institute, National University Hospital, National University Health System, Singapore, Singapore.\nCancer Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore."
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39225869 | 538 | Immuno-related cardio-vascular adverse events associated with immuno-oncological treatments: an under-estimated threat for cancer patients. | Immunotherapy represents an emergent and heterogeneous group of anticancer treatments harnessing the human immune-surveillance system, including immune-checkpoint inhibitor monoclonal antibodies (mAbs), Chimeric Antigen Receptor T Cells (CAR-T) therapy, cancer vaccines and lymphocyte activation gene-3 (LAG-3) therapy. While remarkably effective against several malignancies, these therapies, often in combination with other cancer treatments, have showed unforeseen toxicity, including cardiovascular complications. The occurrence of immuno-mediated adverse (irAEs) events has been progressively reported in the last 10 years. These irAEs present an extended range of severity, from self-limiting to life-threatening conditions. Although recent guidelines in CardioOncology have provided important evidence in managing cancer treatments, they often encompass general approaches. However, a specific focus is required due to the particular etiology, unique risk factors, and associated side effects of immunotherapy. This review aims to deepen the understanding of the prevalence and nature of cardiovascular issues in patients undergoing immunotherapy, offering insights into strategies for risk stratification and management. | [
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"Correale",
"d'Apolito",
"Mutti",
"Giannicola",
"Pirtoli",
"Giordano",
"Labate",
"Macheda",
"Carabetta",
"Abdelwahed",
"Landmesser",
"Tassone",
"Tagliaferri",
"De Rosa",
"Torella"
] | [
"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité Berlin, 12200, Berlin, Germany. [email protected].\nDepartment of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy. [email protected].",
"Medical Oncology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124, Reggio Calabria, Italy.\nSbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA.",
"Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.\nMedical Oncology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124, Reggio Calabria, Italy.",
"Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA.\nDepartment of Applied Sciences and Biotechnology, Università dell'Aquila, L'Aquila, Italy.",
"Medical Oncology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124, Reggio Calabria, Italy.",
"Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA.",
"Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA.\nDepartment of Medical Biotechnology, University of Siena, 53100, Siena, Italy.",
"Unit of Intensive Care Medicine and Anesthesia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124, Reggio Calabria, Italy.",
"Unit of Intensive Care Medicine and Anesthesia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124, Reggio Calabria, Italy.",
"Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.",
"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité Berlin, 12200, Berlin, Germany.\nDZHK (German Centre for Cardiovascular Research), 10785, Berlin, Germany.",
"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité Berlin, 12200, Berlin, Germany.\nDZHK (German Centre for Cardiovascular Research), 10785, Berlin, Germany.\nBerlin Institute of Health (BIH), 10178, Berlin, Germany.",
"Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.\nSbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA.",
"Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.",
"Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.",
"Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy. [email protected]."
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] | [] | 10.565698 | 4.013845 |
39225630 | 539 | Chick Embryo Chorioallantoic Membrane as a Platform for Assessing the In Vivo Efficacy of Chimeric Antigen Receptor T-cell Therapy in Solid Tumors. | The fertilized chicken egg chorioallantoic membrane (CAM), a highly vascularized membrane nourishing the developing embryo, also supports rapid growth of three-dimensional vascularized tumors from engrafted cells and tumor explants. Because murine xenograft models suffer limitations of time, cost, and scalability, we propose CAM tumors as a rapid, efficient screening tool for assessing anti-tumor efficacy of chimeric Ag receptor (CAR) T cells against solid tumors. We tested the efficacy of human epidermal growth factor receptor 2 (HER2)-specific CAR T cells against luminescent, HER2-expressing (FaDu, SCC-47) or HER2-negative (MDA-MB-468) CAM-engrafted tumors. Three days after tumor engraftment, HER2-specific CAR T cells were applied to tumors grown on the CAM. Four days post-CAR T cell treatment, HER2-expressing FaDu and SCC-47 tumors treated with CAR T showed reduced viable cancer cells as assessed by luciferase activity. This reduction in viable tumor cells was confirmed by histology, with lower Ki-67 staining observed in CAR T cell-treated tumors relative to T cell-treated controls. Persistence of CAR T in CAM and tumor tissue 4 days post-treatment was confirmed by CD3 staining. Altogether, our findings support further development of the chick CAM as an in vivo system for rapid, scalable screening of CAR T cell efficacy against human solid tumors. | [
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] | 2024-09-03 | 39 | 39225630 | [
"viable tumor cells",
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"engrafted cells",
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"human solid tumors",
"CAR T",
"solid tumors",
"tumor engraftment",
"tumors",
"tumor explants",
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"CAM",
"HER2-specific CAR T cells",
"Four days post-CAR T cell treatment",
"rapid growth",
"(HER2)-specific CAR T cells",
"human epidermal growth factor receptor",
"anti-tumor efficacy",
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"lower Ki-67 staining",
"CAR",
"murine xenograft models",
"HER2",
"further development",
"CD3 staining",
"HER2-expressing FaDu and SCC-47 tumors",
"treatment",
"The fertilized chicken egg chorioallantoic membrane",
"FaDu"
] | [] | 0 | 10.4049/immunohorizons.2400059 | [
"Nipper",
"Warren",
"Liao",
"Liu",
"Michikawa",
"Porter",
"Wells",
"Villanueva",
"Brasil da Costa",
"Veeramachaneni",
"Villanueva",
"Suzuki",
"Sikora"
] | [
"Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX.",
"Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX.",
"Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX.",
"Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX.",
"Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX.",
"Department of Family and Community Medicine, Baylor College of Medicine, Houston, TX.\nCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.",
"Advanced Technology Cores, Baylor College of Medicine, Houston, TX.",
"Department of Family and Community Medicine, Baylor College of Medicine, Houston, TX.",
"Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX.",
"Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX.",
"Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX.\nAdvanced Technology Cores, Baylor College of Medicine, Houston, TX.",
"Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.\nTexas Children's Hospital, Houston, TX.\nDan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.",
"Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX."
] | [
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] | [] | 9.306191 | 5.277447 |
39224539 | 540 | Targeting chronic lymphocytic leukemia with B-cell activating factor receptor CAR T cells. | The challenge of disease relapsed/refractory (R/R) remains a therapeutic hurdle in chimeric antigen receptor (CAR) T-cell therapy, especially for hematological diseases, with chronic lymphocytic leukemia (CLL) being particularly resistant to CD19 CAR T cells. Currently, there is no approved CAR T-cell therapy for CLL patients. In this study, we aimed to address this unmet medical need by choosing the B-cell activating factor receptor (BAFF-R) as a promising target for CAR design against CLL. BAFF-R is essential for B-cell survival and is consistently expressed on CLL tumors. Our research discovered that BAFF-R CAR T-cell therapy exerted the cytotoxic effects on both CLL cell lines and primary B cells derived from CLL patients. In addition, the CAR T cells exhibited cytotoxicity against CD19-knockout CLL cells that are resistant to CD19 CAR T therapy. Furthermore, we were able to generate BAFF-R CAR T cells from small blood samples collected from CLL patients and then demonstrated the cytotoxic effects of these patient-derived CAR T cells against autologous tumor cells. Given these promising results, BAFF-R CAR T-cell therapy has the potential to meet the long-standing need for an effective treatment on CLL patients. | [
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] | 2024-09-03 | 64 | 39224539 | [
"CD19 CAR T cells",
"primary B cells",
"CD19 CAR T therapy",
"autologous tumor cells",
"CLL patients",
"BAFF-R CAR T cells",
"CLL tumors",
"CLL",
"CD19-knockout CLL cells",
"the CAR T cells",
"BAFF-R CAR T-cell therapy",
"both CLL cell lines",
"B-cell survival",
"chimeric antigen receptor",
"no approved CAR T-cell therapy",
"CAR design",
"these patient-derived CAR T cells",
"CAR",
"hematological diseases",
"chronic lymphocytic leukemia",
"small blood samples",
"the B-cell activating factor receptor",
"(CAR) T-cell therapy",
"disease",
"BAFF-R",
"this unmet medical need",
"cytotoxicity",
"the cytotoxic effects",
"/refractory (R/R",
"a promising target"
] | [
"BAFF‐R",
"B‐cell malignancies",
"CAR T cells",
"chronic lymphocytic leukemia",
"immunotherapy"
] | 0 | 10.1002/mco2.716 | [
"Qie",
"Gadd",
"Shao",
"To",
"Liu",
"Li",
"Rivera-Valentin",
"Yassine",
"Murthy",
"Dronca",
"Kharfan-Dabaja",
"Qin",
"Luo"
] | [
"Regenerative Immunotherapy and CAR-T Translational Research Program Mayo Clinic Jacksonville Florida USA.",
"Regenerative Immunotherapy and CAR-T Translational Research Program Mayo Clinic Jacksonville Florida USA.",
"Regenerative Immunotherapy and CAR-T Translational Research Program Mayo Clinic Jacksonville Florida USA.",
"Regenerative Immunotherapy and CAR-T Translational Research Program Mayo Clinic Jacksonville Florida USA.",
"Department of Cancer Biology Mayo Clinic Jacksonville Florida USA.",
"Regenerative Immunotherapy and CAR-T Translational Research Program Mayo Clinic Jacksonville Florida USA.",
"Department of Pediatric Hematology‑Oncology University of Florida-Jacksonville Jacksonville Florida USA.",
"Division of Hematology and Medical Oncology Department of Internal Medicine Mayo Clinic Jacksonville Florida USA.",
"Division of Hematology and Medical Oncology Department of Internal Medicine Mayo Clinic Jacksonville Florida USA.\nBlood and Marrow Transplantation and Cellular Therapy Program Mayo Clinic Jacksonville Florida USA.",
"Division of Hematology and Medical Oncology Department of Internal Medicine Mayo Clinic Jacksonville Florida USA.",
"Division of Hematology and Medical Oncology Department of Internal Medicine Mayo Clinic Jacksonville Florida USA.\nBlood and Marrow Transplantation and Cellular Therapy Program Mayo Clinic Jacksonville Florida USA.",
"Regenerative Immunotherapy and CAR-T Translational Research Program Mayo Clinic Jacksonville Florida USA.\nDepartment of Cancer Biology Mayo Clinic Jacksonville Florida USA.\nDivision of Hematology and Medical Oncology Department of Internal Medicine Mayo Clinic Jacksonville Florida USA.",
"Regenerative Immunotherapy and CAR-T Translational Research Program Mayo Clinic Jacksonville Florida USA.\nDepartment of Cancer Biology Mayo Clinic Jacksonville Florida USA."
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39224504 | 541 | Targeting the membrane-proximal C2-set domain of CD33 for improved CAR T cell therapy. | Current CD33-targeted immunotherapies typically recognize the membrane-distal V-set domain of CD33. Here, we show that decreasing the distance between T cell and leukemia cell membrane increases the efficacy of CD33 chimeric antigen receptor (CAR) T cells. We therefore generated and optimized second-generation CAR constructs containing single-chain variable fragments from antibodies raised against the membrane-proximal C2-set domain, which bind CD33 regardless of whether the V-set domain is present (CD33 | [
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"AML",
"CAR",
"CD33",
"MT: Novel therapeutic targets and biomarker development Special Issue",
"T cells",
"acute myeloid leukemia",
"adoptive cell therapy",
"chimeric antigen receptor",
"immunotherapy",
"membrane proximity"
] | 0 | 10.1016/j.omton.2024.200854 | [
"Fiorenza",
"Lim",
"Laszlo",
"Kimble",
"Phi",
"Lunn-Halbert",
"Kirchmeier",
"Huo",
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] | [
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.\nFaculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.\nDepartment of Medicine, Division of Hematology and Oncology, University of Washington, Seattle, WA 98195, USA.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.\nFaculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia.",
"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.\nFaculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia.\nDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA."
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39222522 | 542 | Novel Immunotherapy Targets for Relapsed/Refractory B-ALL: A Literature Review. | B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent cancer in United States children. In recent years, immunotherapies using chimeric antigen receptors (CAR T-cells) have improved prognosis for patients with B-ALL. Previous CAR T therapies have used CD19 as a target, but loss of this protein through antigen escape may cause relapse with slim chance of remission. For patients facing relapsed/refractory B-ALL, the need for new targets is evident. In this review, we focus on the KMT2A, IKZF1-related, and DUX4r subgroups of B-ALL, highlighting proven and potential CAR T targets. With a focus on genetics, we discuss chondroitin sulfate proteoglycan 4 as a target in mixed lineage rearranged leukemia and the use of proteomic analysis to locate other B-ALL antigenic surface markers, including the targeting of CD72 within a nanobody-based framework. Additionally, we examine the thymic stromal lymphopoietin receptor as a target in B-ALL with IKAROS family zinc finger 1 deletion across various subgroups. Following this, we propose the adaptation of CD371 as a CAR T-cell target for relapsed/refractory DUX4r B-ALL in the context of promising results from studies in acute myeloid leukemia. Finally, we provide a brief overview of other relevant therapies, including tyrosine kinase inhibitors and a planned universal CAR T for off-the-shelf use, before concluding with a case study that emphasizes the necessity of novel CAR T targets. | [
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] | 2024-09-02 | 1 | 39222522 | [
"novel CAR T targets",
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"chimeric antigen receptors",
"acute myeloid leukemia",
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"B",
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"a planned universal CAR T",
"antigen escape",
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"CAR T-cells",
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"United States children",
"studies",
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"proteomic analysis",
"United States",
"relapsed/refractory B-ALL",
"a CAR T-cell target",
"IKAROS family zinc finger 1 deletion",
"recent years"
] | [] | 0 | null | [
"White",
"Clark",
"Tuller",
"McCurrin",
"Cline",
"Tirado"
] | [
"Texas A and M College of Medicine, College Station, TX.",
"Texas A and M College of Medicine, College Station, TX.",
"Texas A and M College of Medicine, College Station, TX.",
"Texas A and M College of Medicine, College Station, TX.",
"Texas A and M College of Medicine, College Station, TX.",
"Department of Pathology at Stony Brook Medical Center, Stony Brook, NY."
] | [
"39222522"
] | [] | 6.598144 | 6.407419 |
39220881 | 543 | Unlocking T cell exhaustion: Insights and implications for CAR-T cell therapy. | Chimeric antigen receptor T (CAR-T) cell therapy as a form of adoptive cell therapy (ACT) has shown significant promise in cancer treatment, demonstrated by the FDA-approved CAR-T cell therapies targeting CD19 or B cell maturation antigen (BCMA) for hematological malignancies, albeit with moderate outcomes in solid tumors. However, despite these advancements, the efficacy of CAR-T therapy is often compromised by T cell exhaustion, a phenomenon that impedes the persistence and effector function of CAR-T cells, leading to a relapse rate of up to 75% in patients treated with CD19 or CD22 CAR-T cells for hematological malignancies. Strategies to overcome CAR-T exhaustion employ state-of-the-art genomic engineering tools and single-cell sequencing technologies. In this review, we provide a comprehensive understanding of the latest mechanistic insights into T cell exhaustion and their implications for the current efforts to optimize CAR-T cell therapy. These insights, combined with lessons learned from benchmarking CAR-T based products in recent clinical trials, aim to address the challenges posed by T cell exhaustion, potentially setting the stage for the development of tailored next-generation approaches to cancer treatment. | [
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] | 2024-09-02 | 125 | 39220881 | [
"T cell exhaustion",
"adoptive cell therapy",
"CAR-T cell therapy",
"CAR-T cells",
"CD19 or B cell maturation antigen",
"CAR-T therapy",
"CD19 or CD22 CAR-T cells",
"cancer treatment",
"hematological malignancies",
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"moderate outcomes",
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"solid tumors",
"tailored next-generation approaches",
"patients",
"BCMA",
"ACT",
"FDA",
"the latest mechanistic insights",
"lessons",
"Strategies",
"a comprehensive understanding",
"a relapse rate",
"the current efforts",
"the persistence and effector function"
] | [
"CAR-T engineering",
"CAR-T therapy",
"Cancer immunotherapy",
"Combination therapy",
"Single-cell technologies",
"Spatial immune contexture",
"T cell exhaustion",
"Tumor immune microenvironment"
] | 0 | 10.1016/j.apsb.2024.04.022
10.1146/annurev-immunol-090222-110914
10.1038/s41587-023-02060-8 | [
"Xiong",
"Yu",
"Sun"
] | [
"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Science, Wuhan University, Wuhan 430079, China.",
"Department of Radiation and Medical Oncology, Hubei Province Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.",
"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Science, Wuhan University, Wuhan 430079, China."
] | [
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39220130 | 544 | Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy (CAR-T) cell immunotherapy. | Chimeric antigen receptor T-cesll therapy (CAR-T) has achieved groundbreaking advancements in clinical application, ushering in a new era for innovative cancer treatment. However, the challenges associated with implementing this novel targeted cell therapy are increasingly significant. Particularly in the clinical management of solid tumors, obstacles such as the immunosuppressive effects of the tumor microenvironment, limited local tumor infiltration capability of CAR-T cells, heterogeneity of tumor targeting antigens, uncertainties surrounding CAR-T quality, control, and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy. These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach. In this paper, we comprehensively analyze recent preclinical and clinical reports on CAR-T therapy while summarizing crucial factors influencing its efficacy. Furthermore, we aim to identify existing solution strategies and explore their current research status. Through this review article, our objective is to broaden perspectives for further exploration into CAR-T therapy strategies and their clinical applications. | [
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10.1186/s40364-023-00509-1 | [
"Wang",
"Zhou",
"Wu"
] | [
"Department of Institute of Laboratory Animal Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.",
"Department of Institute of Laboratory Animal Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.",
"Ministry of Education and Training, Chengdu Second People's Hospital, Chengdu, China."
] | [
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39220111 | 545 | Smoldering oncolysis by foamy virus carrying CD19 as a CAR target escapes CAR T detection by genomic modification. | Chimeric antigen receptor (CAR) T cells have had limited success against solid tumors. Here, we used an oncolytic foamy virus (oFV) to display a model CAR target antigen (CD19) on tumors in combination with anti-CD19 CAR T cells. We generated oFV-Δ | [
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] | 2024-09-02 | 35 | 39220111 | [
"solid tumors",
"CAR",
"anti-CD19 CAR T cells",
"limited success",
"oFV",
"tumors",
"a model CAR target antigen",
"combination",
"CD19",
"an oncolytic foamy virus",
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"oFV-Δ",
"We",
"we"
] | [
"Apobec",
"CAR T-cell",
"CD19",
"MT: Regular Issue",
"Simian foamy virus",
"cancer",
"oncolytic virotherapy",
"viral mutation",
"viral vectors"
] | 0 | 10.1016/j.omton.2024.200852 | [
"Tonne",
"Budzik",
"Carrasco",
"Ebbert",
"Thompson",
"Nace",
"Kendall",
"Diaz",
"Russell",
"Vile"
] | [
"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.",
"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.",
"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.\nVyriad Inc, Rochester, MN 55901, USA.",
"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.",
"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.",
"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.",
"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.",
"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.",
"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.\nVyriad Inc, Rochester, MN 55901, USA.",
"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.\nDepartment of Immunology, Mayo Clinic, Rochester, MN 55905, USA."
] | [
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] | [] | 10.014754 | 4.025852 |
39217198 | 546 | CD28 hinge used in chimeric antigen receptor (CAR) T-cells exhibits local structure and conformational exchange amidst global disorder. | T-cell therapies based on chimeric antigen receptor (CAR) targeting of a tumor-specific antigen offer hope for patients with relapsed or refractory cancers. CAR hinge and transmembrane regions link antigen recognition domains to intracellular signal transduction domains. Here, we apply biophysical methods to characterize the structure and dynamic properties of the CD28 CAR hinge (CD28H) used in an FDA-approved CD19 CAR for the treatment of B-lineage leukemia/lymphoma. By using nuclear Overhauser effect spectroscopy (NOESY), which detects even transiently occupied structural motifs, we observed otherwise elusive local structural elements amidst overall disorder in CD28H, including a conformational switch from a native β-strand to a 3 | [
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10.1006/abio.2000.4880 | [
"Folimonova",
"Chen",
"Negi",
"Schwieters",
"Li",
"Byrd",
"Taylor",
"Youkharibache",
"Walters"
] | [
"Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.",
"Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.",
"Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.",
"Computational Biomolecular Magnetic Resonance Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.",
"Macromolecular NMR Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.",
"Macromolecular NMR Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.",
"Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.",
"Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.",
"Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA. [email protected]."
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39215816 | 547 | Artificial antigen-presenting cells: the booster for the obtaining of functional adoptive cells. | Adoptive cell therapy (ACT) achieves substantial efficacy in the treatment of hematological malignancies and solid tumours, while enormous endeavors have been made to reduce relapse and extend the remission duration after ACT. For the genetically engineered T cells, their functionality and long-term anti-tumour potential depend on the specificity of the T cell receptor (TCR) or chimeric antigen receptor (CAR). In addition, the therapeutic benefit is directly to sufficient activation and proliferation of engineered T cells. Artificial antigen-presenting cells (aAPCs), as powerful boosters for ACT, have been applied to provide sustained stimulation of the cognate antigen and facilitate the expansion of sufficient T cells for infusion. In this review, we summarize the aAPCs used to generate effector cells for ACT and underline the mechanism by which aAPCs enhance the functionality of the effector cells. The manuscript includes investigations ranging from basic research to clinical trials, which we hope will highlight the importance of aAPCs and provide guidance for novel strategies to improve the effectiveness of ACT. | [
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10.1038/nbt955 | [
"Li",
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"Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People's Republic of China.",
"Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People's Republic of China.",
"Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People's Republic of China. [email protected]."
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39213422 | 548 | Local radiation enhances systemic CAR T-cell efficacy by augmenting antigen crosspresentation and T-cell infiltration. | Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CART-19) represents a significant advance in the treatment of patients with relapsed or refractory CD19+ B-cell lymphomas. However, a significant portion of patients either relapse or fail to respond. Moreover, many patients have symptomatic disease, requiring bridging radiation therapy (RT) during the period of CAR T-cell manufacturing. To investigate the impact of 1 to 2 fractions of low-dose RT on CART-19 treatment response, we developed a mouse model using A20 lymphoma cells for CART-19 therapy. We found that low-dose fractionated RT had a positive effect on generating abscopal systemic antitumor responses beyond the irradiated site. The combination of RT with CART-19 therapy resulted in additive effects on tumor growth in irradiated masses. Notably, a significant additional increase in antitumor effect was observed in nonirradiated tumors. Mechanistically, our results validate activation of the cyclic guanosine adenosine synthetase/stimulator of interferon genes pathway, tumor-associated antigen crosspriming, and elicitation of epitope spreading. Collectively, our findings suggest that RT may serve as an optimal priming and bridging modality for CAR T-cell therapy, overcoming treatment resistance and improving clinical outcomes in patients with CD19+ hematologic malignancies. | [
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] | 2024-08-31 | 62 | 39213422 | [
"CART-19 treatment response",
"antitumor effect",
"CART-19 therapy",
"A20 lymphoma cells",
"RT",
"abscopal systemic antitumor responses",
"radiation therapy",
"CD19+ hematologic malignancies",
"many patients",
"additive effects",
"patients",
"treatment resistance",
"tumor growth",
"nonirradiated tumors",
"CAR T-cell therapy",
"CD19",
"CAR T-cell manufacturing",
"interferon genes",
"low-dose fractionated RT",
"low-dose RT",
"irradiated masses",
"symptomatic disease",
"clinical outcomes",
"relapsed or refractory CD19+ B-cell lymphomas",
"Chimeric antigen receptor",
"CAR) T-cell therapy",
"CART-19",
"tumor-associated antigen",
"interferon",
"activation"
] | [] | 0 | 10.1182/bloodadvances.2024012599 | [
"Kostopoulos",
"Costabile",
"Krimitza",
"Beghi",
"Goia",
"Perales-Linares",
"Thyfronitis",
"LaRiviere",
"Chong",
"Schuster",
"Maity",
"Koumenis",
"Plastaras",
"Facciabene"
] | [
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.\nCenter for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA.\nDepartment of Biological Applications and Technology, University of Ioannina, Ioannina, Greece.",
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.\nCenter for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA.",
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.\nCenter for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA.",
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.\nCenter for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA.",
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.",
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.",
"Department of Biological Applications and Technology, University of Ioannina, Ioannina, Greece.",
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.",
"Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA.\nDivision of Hematology and Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.\nLymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.",
"Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA.\nDivision of Hematology and Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.\nLymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.",
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.",
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.",
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.",
"Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.\nCenter for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA.\nThe Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA."
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39213364 | 549 | Multi-armored allogeneic MUC1 CAR T cells enhance efficacy and safety in triple-negative breast cancer. | Solid tumors, such as triple-negative breast cancer (TNBC), are biologically complex due to cellular heterogeneity, lack of tumor-specific antigens, and an immunosuppressive tumor microenvironment (TME). These challenges restrain chimeric antigen receptor (CAR) T cell efficacy, underlining the importance of armoring. In solid cancers, a localized tumor mass allows alternative administration routes, such as intratumoral delivery with the potential to improve efficacy and safety but may compromise metastatic-site treatment. Using a multi-layered CAR T cell engineering strategy that allowed a synergy between attributes, we show enhanced cytotoxic activity of MUC1 CAR T cells armored with PD1 | [
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] | 2024-08-31 | 1 | 39210780 | [] | [
"CAR-T bystander effects",
"CAR-T cell therapy",
"antigen density",
"endogenous immune response",
"epitope spreading",
"solid cancer",
"tumor antigen heterogeneity"
] | 0 | 10.1080/14712598.2024.2399141 | [
"Klampatsa"
] | [
"Thoracic Oncology Immunotherapy Group, The Institute of Cancer Research, Division of Cancer Therapeutics, London, UK."
] | [
"39210780"
] | [] | 32.954296 | 7.548981 |
39209767 | 551 | Immune modulatory microRNAs in tumors, their clinical relevance in diagnosis and therapy. | The importance of the immune system in regulating tumor growth by inducing immune cell-mediated cytotoxicity associated with patients' outcomes has been highlighted in the past years by an increasing life expectancy in patients with cancer on treatment with different immunotherapeutics. However, tumors often escape immune surveillance, which is accomplished by different mechanisms. Recent studies demonstrated an essential role of small non-coding RNAs, such as microRNAs (miRNAs), in the post-transcriptional control of immune modulatory molecules. Multiple methods have been used to identify miRNAs targeting genes involved in escaping immune recognition including miRNAs targeting CTLA-4, PD-L1, HLA-G, components of the major histocompatibility class I antigen processing machinery (APM) as well as other immune response-relevant genes in tumors. Due to their function, these immune modulatory miRNAs can be used as (1) diagnostic and prognostic biomarkers allowing to discriminate between tumor stages and to predict the patients' outcome as well as response and resistance to (immuno) therapies and as (2) therapeutic targets for the treatment of tumor patients. This review summarizes the role of miRNAs in tumor-mediated immune escape, discuss their potential as diagnostic, prognostic and predictive tools as well as their use as therapeutics including alternative application methods, such as chimeric antigen receptor T cells. | [
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] | 0 | 10.1136/jitc-2024-009774
10.1158/2159-8290.CD-21-1059
10.1126/science.1203486
10.1016/j.immuni.2004.07.017
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10.1038/ncomms11406 | [
"Vaxevanis",
"Bachmann",
"Seliger"
] | [
"Institute for Medical Immunology, Martin Luther University Halle Wittenberg, Halle, Germany.",
"Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.",
"Institute for Medical Immunology, Martin Luther University Halle Wittenberg, Halle, Germany [email protected].\nInstitute for Translational Immunology, Brandenburg Medical School Theodor Fontane, Brandenburg, Germany.\nFraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany.\nInstitute of Translational Immunology, Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, Brandenburg, Germany."
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39206402 | 552 | The Art of Bioimmunogenomics (BIGs) 5.0 in CAR-T Cell Therapy for Lymphoma Management. | Lymphoma, the most predominant neoplastic disorder, is divided into Hodgkin and Non-Hodgkin Lymphoma classifications. Immunotherapeutic modalities have emerged as essential methodologies in combating lymphoid malignancies. Chimeric Antigen Receptor (CAR) T cells exhibit promising responses in chemotherapy-resistant B-cell non-Hodgkin lymphoma cases.
This comprehensive review delineates the advancement of CAR-T cell therapy as an immunotherapeutic instrument, the selection of lymphoma antigens for CAR-T cell targeting, and the conceptualization, synthesis, and deployment of CAR-T cells. Furthermore, it encompasses the advantages and disadvantages of CAR-T cell therapy and the prospective horizons of CAR-T cells from a computational research perspective. In order to improve the design and functionality of artificial CARs, there is a need for TCR recognition investigation, followed by the implementation of a quality surveillance methodology.
Various lymphoma antigens are amenable to CAR-T cell targeting, such as CD19, CD20, CD22, CD30, the kappa light chain, and ROR1. A notable merit of CAR-T cell therapy is the augmentation of the immune system's capacity to generate tumoricidal activity in patients exhibiting chemotherapy-resistant lymphoma. Nevertheless, it also introduces manufacturing impediments that are laborious, technologically demanding, and financially burdensome. Physical, physicochemical, and physiological limitations further exacerbate the challenge of treating solid neoplasms with CAR-T cells.
While the efficacy and safety of CAR-T cell immunotherapy remain subjects of fervent investigation, the promise of this cutting-edge technology offers valuable insights for the future evolution of lymphoma treatment management approaches. Moreover, CAR-T cell therapies potentially benefit patients, motivating regulatory bodies to foster international collaboration. | [
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10.1080/13696998.2019.1582059 | [
"Anurogo",
"Luthfiana",
"Anripa",
"Fauziah",
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"Rahmah",
"Ratnawati",
"Wargasetia",
"Pratiwi",
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"Sholichah",
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"Ikrar",
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"International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan.\nFaculty of Medicine and Health Sciences, Muhammadiyah University of Makassar, Makassar, South Sulawesi, 90221, Indonesia.",
"Bioinformatics Research Center, Indonesian Institute of Bioinformatics (INBIO), Malang, East Java, 65162, Indonesia.",
"Department of Environmental Science, Dumoga University, Kotamobagu, South Sulawesi, 95711, Indonesia.\nFaculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.",
"MSc Program in Tropical Medicine, Kaohsiung Medical University, Kaohsiung City, 807378, Taiwan.",
"National Research and Innovation Agency (BRIN), Central Jakarta, 10340, Indonesia.\nIKIFA College of Health Sciences, East Jakarta, Special Capital Region of Jakarta, 13470, Indonesia.",
"Department of Digital Health, School of Medicine, Tehran University of Medical Sciences, Tehran, 1416634793, Iran.\nFaculty of Medicine, Muhammadiyah University of Surabaya, Surabaya, East Java, 60113, Indonesia.",
"Faculty of Medicine, Maranatha Christian University, Bandung, West Java, 40164, Indonesia.",
"Faculty of Medicine, Maranatha Christian University, Bandung, West Java, 40164, Indonesia.",
"Department of Biology and Pathobiology, Faculty of Medicine, Tanjungpura University, Pontianak, West Kalimantan, 78115, Indonesia.",
"National Research and Innovation Agency (BRIN), Central Jakarta, 10340, Indonesia.",
"Department of Biotechnology, Postgraduate School of Gadjah Mada University, Yogyakarta, 55284, Indonesia.",
"Community Health Center (Puskesmas) Temon 1, Kulon Progo, Special Region of Yogyakarta, 55654, Indonesia.",
"Director of Members-at-Large, International Association of Medical Regulatory Authorities (IAMRA), Texas, 76039, USA.\nAivita Biomedical Inc., Irvine, California, 92612, USA.\nChairman of Medical Council, The Indonesian Medical Council (KKI), Central Jakarta, 10350, Indonesia.\nAdjunct Professor, School of Military Medicine, The Republic of Indonesia Defense University (RIDU), Jakarta Pusat, 10440, Indonesia.\nDepartment of Pharmacology, Faculty of Medicine, Malahayati University, Bandar Lampung, Lampung, 35152, Indonesia.",
"International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan.\nLocus Cell Co., LTD., Xizhi Dist., New Taipei City, 221, Taiwan.",
"International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan.\nDepartment of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan.\nDepartment of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, 110301, Taiwan."
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39201242 | 553 | A Comprehensive ddPCR Strategy for Sensitive and Reliable Monitoring of CAR-T Cell Kinetics in Clinical Applications. | In this study, we present the design, implementation, and successful use of digital droplet PCR (ddPCR) for the monitoring of chimeric antigen receptor T-cell (CAR-T) expansion in patients with B-cell malignancies treated with different CAR-T products at our clinical center. Initially, we designed a specific and highly sensitive ddPCR assay targeting the junction between the 4-1BB and CD3ζ domains of tisa-cel, normalized with | [
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"Porret"
] | [
"Department of Hematology and Central Hematological Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.\nDepartment for BioMedical Research, University of Bern, 3008 Bern, Switzerland.",
"Department of Hematology and Central Hematological Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.",
"Department of Hematology and Central Hematological Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.",
"Service and Central Laboratory of Hematology, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.",
"Department of Medical Oncology and Hematology, University Hospital Zurich, 8091 Zurich, Switzerland.\nDepartment of Hematology, University Hospital of Basel, 4031 Basel, Switzerland.\nLaboratory Medicine, Diagnostic Hematology, 4031 Basel, Switzerland.",
"Department for BioMedical Research, University of Bern, 3008 Bern, Switzerland.",
"Department of Medical Oncology, Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.\nCenter for Hemato-Oncology, University Cancer Center, 3010 Bern, Switzerland.",
"Department of Medical Oncology, Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.\nCenter for Hemato-Oncology, University Cancer Center, 3010 Bern, Switzerland.",
"Department of Hematology and Central Hematological Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.\nDepartment for BioMedical Research, University of Bern, 3008 Bern, Switzerland."
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39200107 | 554 | Evaluation of Anti-CAR Linker mAbs for CAR T Monitoring after BiTEs/bsAbs and CAR T-Cell Pretreatment. | For the monitoring of chimeric antigen receptor (CAR) T-cell therapies, antigen-based CAR detection methods are usually applied. However, for each target-antigen, a separate detection system is required. Furthermore, when monitored CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods produce false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment promise a universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19-targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel, the sensitivity was significantly lower compared to that for antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel, or Ide-cel, respectively. Cilta-cel (containing a monomeric G | [
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10.1111/bjh.19001 | [
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] | [
"Medical Faculty, Institute of Clinical Immunology, Leipzig and University of Leipzig Medical Center, Leipzig University, 04103 Leipzig, Germany.",
"Medical Faculty, Institute of Clinical Immunology, Leipzig and University of Leipzig Medical Center, Leipzig University, 04103 Leipzig, Germany.",
"Medical Faculty, Institute of Clinical Immunology, Leipzig and University of Leipzig Medical Center, Leipzig University, 04103 Leipzig, Germany.",
"Fraunhofer Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany.",
"Medical Faculty, Institute of Clinical Immunology, Leipzig and University of Leipzig Medical Center, Leipzig University, 04103 Leipzig, Germany.",
"Department of Hematology and Cell Therapy, Medical Faculty, Leipzig and University of Leipzig Medical Center, Leipzig University, 04103 Leipzig, Germany.\nUniversity Cancer Center Leipzig (UCCL), Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany.",
"Department of Hematology and Cell Therapy, Medical Faculty, Leipzig and University of Leipzig Medical Center, Leipzig University, 04103 Leipzig, Germany.\nUniversity Cancer Center Leipzig (UCCL), Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany.",
"Department of Hematology and Cell Therapy, Medical Faculty, Leipzig and University of Leipzig Medical Center, Leipzig University, 04103 Leipzig, Germany.\nUniversity Cancer Center Leipzig (UCCL), Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany.",
"Department of Pediatric Immunology, Pediatric Rheumatology and Infectiology, Clinic and Polyclinic for Pediatric and Adolescent Medicine, Leipzig and University of Leipzig Medical Center, Leipzig University, 04103 Leipzig, Germany.",
"Medical Faculty, Institute of Clinical Immunology, Leipzig and University of Leipzig Medical Center, Leipzig University, 04103 Leipzig, Germany.\nFraunhofer Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany.\nUniversity Cancer Center Leipzig (UCCL), Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany.",
"Medical Faculty, Institute of Clinical Immunology, Leipzig and University of Leipzig Medical Center, Leipzig University, 04103 Leipzig, Germany.\nUniversity Cancer Center Leipzig (UCCL), Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany."
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39199683 | 555 | CAR-T Cells in the Treatment of Nervous System Tumors. | Chimeric antigen receptor T cells (CAR-Ts) have shown a remarkable efficacy in hematological malignancies but limited responses in solid tumors. Among solid tumors, CAR-T cell therapy has been particularly explored in brain tumors. CAR-T cells have shown a limited clinical efficacy in various types of brain tumors due to several factors that have hampered their activity, including tumor antigen heterogeneity, the limited access of CAR-T cells to brain tumor cells, limited CAR-T cell trafficking and in vivo persistence and the presence of a highly immunosuppressive tumor microenvironment. Despite these considerations, some recent studies have shown promising antitumor activity of GD2-CAR-T cells on diffuse midline gliomas and neuroblastomas and of CARv3-TEAM-E cells in glioblastomas. However, strategies are required to improve the effect of CAR-T cells in brain tumors, including advanced CAR-T cell design with multiple antigenic targeting and incorporation of combination therapies. | [
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39199421 | 556 | CAR-NK Cell Therapy: A Transformative Approach to Overcoming Oncological Challenges. | The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. This review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors. | [
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] | 2024-08-31 | 115 | 39199421 | [
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10.1186/s13287-022-02769-4 | [
"Li",
"Wang",
"Zhang",
"Aziz",
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] | [
"China Key Laboratory for Early Diagnosis and Biotherapy of Malignant Tumors in Children and Women, Dalian Women and Children's Medical Group, Dalian 116012, China.\nDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.",
"China Key Laboratory for Early Diagnosis and Biotherapy of Malignant Tumors in Children and Women, Dalian Women and Children's Medical Group, Dalian 116012, China.",
"The Second Affiliated Hospital of Harbin Medical University, Harbin 151801, China.",
"China Key Laboratory for Early Diagnosis and Biotherapy of Malignant Tumors in Children and Women, Dalian Women and Children's Medical Group, Dalian 116012, China.",
"China Key Laboratory for Early Diagnosis and Biotherapy of Malignant Tumors in Children and Women, Dalian Women and Children's Medical Group, Dalian 116012, China."
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39196960 | 557 | Next-generation CAR T cell therapies for glioblastoma. | Interim results from two phase 1 trials demonstrate progress in the use of chimeric antigen receptor (CAR) T cell therapy for recurrent glioblastoma (GBM). | [
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] | 2024-08-29 | 1 | 39196960 | [
"T cell therapy",
"chimeric antigen receptor",
"recurrent glioblastoma",
"Interim results",
"progress",
"CAR",
"GBM",
"1 trials",
"the use",
"two phase",
"1",
"two"
] | [] | 0 | 10.1126/scitranslmed.adp2660 | [
"Bernstock",
"Gerstl",
"Valdés",
"Friedman",
"Chiocca"
] | [
"Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.\nDepartment of Neurosurgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.\nDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.",
"Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.",
"Department of Neurosurgery, University of Texas Medical Branch, Galveston, TX 77555, USA.",
"Division of Pediatrics, Neuro-Oncology Section, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.",
"Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA."
] | [
"39196960"
] | [] | 9.992397 | 7.369482 |
39196390 | 558 | IL-21- and CXCL9-engineered GPC3-specific CAR-T cells combined with PD-1 blockade enhance cytotoxic activities against hepatocellular carcinoma. | The application of CAR-T cells in solid tumors poses several challenges, including poor T cell homing ability, limited infiltration of T cells and an immunosuppressive tumor environment. In this study, we developed a novel approach to address these obstacles by designing GPC3-specific CAR-T cell that co-express IL-21 and CXCL9 (21 × 9 GPC3 CAR-T cells) and blocking the PD-1 expression on it. The proliferation, cell phenotype, cytokine secretion and cell migration of indicated CAR-T cells were evaluated in vitro. The cytotoxic activities of genetically engineered CAR-T cells were accessed in vitro and in vivo. Compared to conventional GPC3 CAR-T cells, the 21 × 9 GPC3 CAR-T cells demonstrated superior proliferation, cytokine secretion and chemotaxis capabilities in vitro. Furthermore, when combined with PD-1 blockade, the 21 × 9 GPC3 CAR-T cells exhibited enhanced proliferation, cytokine secretion and enrichment of effector T cells such as CTL, NKT and TEM cells. In xenograft tumor models, the PD-1 blocked 21 × 9 GPC3 CAR-T cells effectively suppressed HCC xenograft growth and increased T cell infiltration. Overall, our study successfully generated GPC3 CAR-T cells expressing both IL-21 and CXCL9, demonstrated that combining PD-1 blockade can further enhance CAR-T cell function by promoting proliferation, cytokine secretion, chemotaxis and antitumor activity. These findings present a hopeful and potentially effective strategy for GPC3-positive HCC patients. | [
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] | 2024-08-28 | 39 | 39196390 | [
"T cells",
"increased T cell infiltration",
"poor T cell homing ability",
"effector T cells",
"cell migration",
"TEM cells",
"cell phenotype",
"conventional GPC3 CAR-T cells",
"GPC3 CAR-T cells",
"CAR-T cell function",
"CAR-T cells",
"cytokine secretion",
"indicated CAR-T cells",
"9 GPC3 CAR-T cells",
"xenograft tumor models",
"enhanced proliferation",
"superior proliferation",
"GPC3-specific CAR-T cell",
"secretion",
"HCC xenograft growth",
"genetically engineered CAR-T cells",
"solid tumors",
"proliferation",
"PD-1 blockade",
"GPC3-positive HCC patients",
"several challenges",
"limited infiltration",
"IL-21",
"CXCL9",
"chemotaxis capabilities"
] | [
"CAR-T",
"CXCL9",
"GPC3",
"HCC",
"IL-21",
"PD-1"
] | 0 | 10.1007/s10238-024-01473-2 | [
"Chen",
"Gong",
"Liu",
"Xie",
"Ye",
"Lin",
"Wang",
"Zheng",
"Liu",
"Sun"
] | [
"Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.",
"Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.",
"Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.",
"Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.",
"Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.",
"Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.",
"Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.",
"Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.\nXiamen Humanity Hospital, Xiamen, 361003, China.",
"Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.",
"Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China. [email protected].\nDepartment of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China. [email protected]."
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] | [] | 9.653957 | 6.007149 |
39195306 | 559 | Venous Thromboembolism Risk in Hematological Malignancies Post-Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: A Meta-Analysis of Phase 2 and Phase 3 Clinical Trials. | Chimeric Antigen Receptor T-cell (CAR-T) therapy uses genetically engineered T-cells with specific binding sites. This therapy allows for tumor specificity and durable treatment responses for patients with hematological malignancies. In this review, we study the risk of venous thromboembolism (VTE) associated with CAR-T therapy. We searched the National Institutes of Health library, Cochrane Library Databases, ClinicalTrials.gov database, and medical literature search engines PubMed and Google Scholar for Phase 2 and Phase 3 drug-efficacy and safety trials to determine the aggregate incidence and risk of VTE treated with CAR-T. Of 1127 search results, nine studies were identified and included in our meta-analysis. Of the 1017 patients who received therapy, 805 patients (79.15%) experienced some degree of CRS, and 122 patients (11.9%) experienced severe CRS (higher than grade 3). Only three out of one thousand and seventeen patients were reported to have experienced venous thromboembolism. Our study did not find a statistically significant association between increased VTE incidence (OR = 0.0005, 95% CI [0.0001, 0.0017]) and CRS/ICANS ( | [
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10.1097/CCM.0000000000004971 | [
"Chitkara",
"Sreenivasan",
"Yin",
"Rai",
"Sadashiv"
] | [
"Department of Internal Medicine, University of California, Riverside, CA 92521, USA.",
"Department of Internal Medicine, Allegheny Health Consortium, Pittsburgh, PA 15222, USA.",
"Allegheny Singer Research Institute, Pittsburgh, PA 15212, USA.",
"Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA.",
"Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA."
] | [
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] | [] | 6.018347 | 4.21557 |
39194355 | 560 | Clinical outcomes and microenvironment profiling in relapsed/refractory multiple myeloma patients with extramedullary disease receiving anti-BCMA CAR T-cell-based therapy. | Relapsed/refractory multiple myeloma patients with extramedullary disease (EMD) have unfavorable prognosis and lack effective therapy. Chimeric antigen receptor (CAR) T-cell activities in EMD have yet to be determined; how EMD-specific microenvironment influences the clinical outcomes of CAR T-cell therapy remains of great interest. In this prospective cohort study, patients with histologically confirmed extra-osseous EMD were enrolled and treated with combined anti-BCMA and anti-CD19 CAR T-cell therapy from May 2017 to September 2023. Thirty-one patients were included in the study. Overall response occurred in 90.3% of medullary disease and 64.5% of EMD (p = .031). Discrepancies in treatment response were noted between medullary and extramedullary diseases, with EMD exhibiting suboptimal and delayed response, as well as shortened response duration. With a median follow-up of 25.3 months, the median progression-free and overall survival were 5.0 and 9.7 months, respectively. Landmark analysis demonstrated that progression within 6 months post-infusion is strongly associated with an increased risk of death (HR = 4.58; p = .029). Compared with non-EMD patients, patients with EMD showed inferior survival outcomes. Unique CAR-associated local toxicities at EMD were seen in 22.6% patients and correlated with the occurrence and severity of systemic cytokine release syndrome. To the cutoff date, 65% treated patients experienced EMD progression, primarily in the form of BCMA | [
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] | 2024-08-28 | 1 | 39194355 | [
"EMD progression",
"EMD",
"non-EMD patients",
"patients",
"extramedullary disease",
"medullary disease",
"Overall response",
"non-EMD",
"treatment response",
"histologically confirmed extra-osseous EMD",
"shortened response duration",
"anti-CD19 CAR T-cell therapy",
"effective therapy",
"inferior survival outcomes",
"progression",
"systemic cytokine release syndrome",
"65% treated patients",
"CAR T-cell therapy",
"Relapsed/refractory multiple myeloma patients",
"22.6% patients",
"unfavorable prognosis",
"Chimeric antigen receptor",
"Unique CAR-associated local toxicities",
"medullary and extramedullary diseases",
"how EMD-specific microenvironment influences",
"Landmark analysis",
"great interest",
"suboptimal and delayed response",
"severity",
"death"
] | [] | 0 | 10.1002/ajh.27469 | [
"Qi",
"Li",
"Qi",
"Zhu",
"Cheng",
"Chen",
"Yan",
"Li",
"Sang",
"Fei",
"Gu",
"Miao",
"Huang",
"Wang",
"Qiu",
"Qiao",
"Pan",
"Shi",
"Wang",
"Li",
"Zheng",
"Xu",
"Cao"
] | [
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Department of Hematology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.",
"Department of Hematology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, China.",
"Department of Hematology, The First People's Hospital of Yancheng, Yancheng, China.",
"Department of Hematology, The Affiliated Hospital of Nantong University, Nantong, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nJiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, China.\nCenter of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nJiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, China.\nCenter of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nJiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, China.\nCenter of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China.",
"Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China.\nDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.\nJiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China."
] | [
"39194355"
] | [] | 5.181842 | 5.75988 |
39193002 | 561 | B7 homolog 3 in pancreatic cancer. | Despite advances in cancer treatment, pancreatic cancer (PC) remains a disease with high mortality rates and poor survival outcomes. The B7 homolog 3 (B7-H3) checkpoint molecule is overexpressed among many malignant tumors, including PC, with low or absent expression in healthy tissues. By modulating various immunological and nonimmunological molecular mechanisms, B7-H3 may influence the progression of PC. However, the impact of B7-H3 on the survival of patients with PC remains a subject of debate. Still, most available scientific data recognize this molecule as a suppressive factor to antitumor immunity in PC. Furthermore, it has been demonstrated that B7-H3 stimulates the migration, invasion, and metastasis of PC cells, and enhances resistance to chemotherapy. In preclinical models of PC, B7-H3-targeting monoclonal antibodies have exerted profound antitumor effects by increasing natural killer cell-mediated antibody-dependent cellular cytotoxicity and delivering radioisotopes and cytotoxic drugs to the tumor site. Finally, PC treatment with B7-H3-targeting antibody-drug conjugates and chimeric antigen receptor T cells is being tested in clinical studies. This review provides a comprehensive analysis of all PC-related studies in the context of B7-H3 and points to deficiencies in the current data that should be overcome by future research. | [
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] | [
"B7 homolog 3",
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] | 0 | 10.3748/wjg.v30.i31.3654 | [
"Perovic",
"Dusanovic Pjevic",
"Perovic",
"Grk",
"Rasic",
"Milickovic",
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"Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.",
"Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.",
"Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.",
"Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.",
"Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.",
"Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia \"Dr. Vukan Cupic\", Belgrade 11000, Serbia.\nFaculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.",
"Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia \"Dr. Vukan Cupic\", Belgrade 11000, Serbia.",
"Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia \"Dr. Vukan Cupic\", Belgrade 11000, Serbia. [email protected]."
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39192973 | 562 | Good manufacturing practice-grade generation of CD19 and CD123-specific CAR-T cells using piggyBac transposon and allogeneic feeder cells in patients diagnosed with B-cell non-Hodgkin lymphoma and acute myeloid leukemia. | The non-viral production of CAR-T cells through electroporation of transposon DNA plasmids is an alternative approach to lentiviral/retroviral methods. This method is particularly suitable for early-phase clinical trials involving novel types of CAR-T cells. The primary disadvantage of non-viral methods is the lower production efficiency compared to viral-based methods, which becomes a limiting factor for CAR-T production, especially in chemotherapy-pretreated lymphopenic patients.
We describe a good manufacturing practice (GMP)-compliant protocol for producing CD19 and CD123-specific CAR-T cells based on the electroporation of transposon vectors. The lymphocytes were purified from the blood of patients undergoing chemotherapy for B-NHL or AML and were electroporated with piggyBac transposon encoding CAR19 or CAR123, respectively. Electroporated cells were then polyclonally activated by anti-CD3/CD28 antibodies and a combination of cytokines (IL-4, IL-7, IL-21). The expansion was carried out in the presence of irradiated allogeneic blood-derived mononuclear cells (i.e., the feeder) for up to 21 days.
Expansion in the presence of the feeder enhanced CAR-T production yield (4.5-fold in CAR19 and 9.3-fold in CAR123). Detailed flow-cytometric analysis revealed the persistence of early-memory CAR-T cells and a low vector-copy number after production in the presence of the feeder, with no negative impact on the cytotoxicity of feeder-produced CAR19 and CAR123 T cells. Furthermore, large-scale manufacturing of CAR19 carried out under GMP conditions using PBMCs obtained from B-NHL patients (starting number=200x10e6 cells) enabled the production of >50x10e6 CAR19 in 7 out of 8 cases in the presence of the feeder while only in 2 out of 8 cases without the feeder.
The described approach enables GMP-compatible production of sufficient numbers of CAR19 and CAR123 T cells for clinical application and provides the basis for non-viral manufacturing of novel experimental CAR-T cells that can be tested in early-phase clinical trials. This manufacturing approach can complement and advance novel experimental immunotherapeutic strategies against human hematologic malignancies. | [
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"non-viral manufacturing",
"non-viral methods",
"number=200x10e6 cells",
"Electroporated cells",
"production",
"CAR19 and CAR123 T cells",
"novel experimental CAR-T cells",
"novel experimental immunotherapeutic strategies",
"CAR19",
"CAR-T cells",
"CAR-T production",
"enhanced CAR-T production yield",
"feeder-produced CAR19 and CAR123 T cells",
"The non-viral production",
"novel types",
"irradiated allogeneic blood-derived mononuclear cells",
"early-memory CAR-T cells",
"clinical application",
"CD123-specific CAR-T cells",
"transposon DNA plasmids",
"transposon vectors",
"patients",
"sufficient numbers",
"human hematologic malignancies",
"anti-CD3/CD28",
"GMP conditions",
"early-phase clinical trials",
"CAR123",
"piggyBac transposon",
"the lower production efficiency"
] | [
"CAR-T cells",
"PiggyBac PB transposon",
"electroporation",
"leukemia",
"lymphoma"
] | 0 | 10.3389/fimmu.2024.1415328
10.1111/bjh.18831
10.1038/mt.2010.141
10.1097/CJI.0b013e3181b2914c
10.1089/hum.2009.114
10.1038/s41392-021-00487-6
10.3389/fimmu.2022.867013
10.1016/j.omtm.2021.08.006
10.1016/j.jcyt.2020.08.005
10.1016/j.jcyt.2017.10.001
10.1016/j.omtm.2020.06.024
10.1073/pnas.1305987110
10.1073/pnas.1008322108
10.1096/fj.02-0859fje
10.1016/j.bbamem.2010.10.009
10.1038/mtna.2015.59
10.1517/17425247.2016.1121990
10.1016/j.ymthe.2016.12.009
10.2174/156652310791823461
10.1016/j.omtm.2021.03.011
10.1016/j.exphem.2007.04.007
10.1016/j.omtm.2017.12.003
10.1016/j.jcyt.2014.05.022
10.1016/j.jcyt.2015.05.013 | [
"Mucha",
"Štach",
"Kaštánková",
"Rychlá",
"Vydra",
"Lesný",
"Otáhal"
] | [
"Institute of Hematology and Blood Transfusion, Prague, Czechia.\nFaculty of Science, Charles University, Prague, Czechia.",
"Institute of Hematology and Blood Transfusion, Prague, Czechia.\nFaculty of Science, Charles University, Prague, Czechia.",
"Institute of Hematology and Blood Transfusion, Prague, Czechia.",
"Institute of Hematology and Blood Transfusion, Prague, Czechia.",
"Institute of Hematology and Blood Transfusion, Prague, Czechia.",
"Institute of Hematology and Blood Transfusion, Prague, Czechia.",
"Institute of Hematology and Blood Transfusion, Prague, Czechia."
] | [
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39192970 | 563 | Acute T-cell lymphoblastic leukemia: chimeric antigen receptor technology may offer a new hope. | Acute lymphoblastic leukemia (ALL) is a prevalent malignancy affecting the hematopoietic system, encompassing both B-cell ALL (B-ALL) and T-cell ALL (T-ALL). T-ALL, characterized by the proliferation of T-cell progenitors in the bone marrow, presents significant treatment challenges, with patients often experiencing high relapse rates and poor long-term survival despite advances in chemotherapy and hematopoietic stem cell transplantation (HSCT). This review explores the pathogenesis and traditional treatment strategies of T-ALL, emphasizing the promising potential of chimeric antigen receptor (CAR) technology in overcoming current therapeutic limitations. CAR therapy, leveraging genetically modified immune cells to target leukemia-specific antigens, offers a novel and precise approach to T-ALL treatment. The review critically analyzes recent developments in CAR-T and CAR-NK cell therapies, their common targets, optimization strategies, clinical outcomes, and the associated challenges, providing a comprehensive overview of their clinical prospects in T-ALL treatment. | [
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"Jing",
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"Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China.",
"Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China.",
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"Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.",
"Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China."
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39192467 | 564 | The potential of γδ CAR and TRuC T cells: An unearthed treasure. | Recent years have witnessed the success of αβ T cells engineered to express chimeric antigen receptors (CARs) in treating haematological cancers. CARs combine the tumour antigen binding capability of antibodies with the signalling functions of the T-cell receptor (TCR) ζ chain and co-stimulatory receptors. Despite the success, αβ CAR T cells face limitations. Possible solutions would be the use of γδ T cells and new chimeric receptors, such as TCR fusion constructs (TRuCs). Notably, γδ CAR T cells are gaining traction in pre-clinical and clinical studies, demonstrating a promising safety profile in several pilot studies. This review delves into the current understanding of γδ CAR and TCR fusion construct T cells, exploring the opportunities and challenges they present for cancer treatment. | [
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] | 2024-08-28 | 1 | 39192467 | [
"γδ CAR T cells",
"γδ T cells",
"T cells",
"αβ CAR T cells",
"αβ T cells",
"co-stimulatory receptors",
"γδ CAR",
"chimeric antigen receptors",
"new chimeric receptors",
"TCR fusion",
"several pilot studies",
"CAR",
"pre-clinical and clinical studies",
"haematological cancers",
"TCR",
"cancer treatment",
"ζ chain",
"CARs",
"the T-cell receptor",
"Recent years",
"Possible solutions",
"the tumour antigen binding capability",
"challenges",
"traction",
"a promising safety profile",
"limitations",
"the current understanding",
"the signalling functions",
"the success",
"the opportunities"
] | [
"CAR",
"Immunotherapy",
"TRuC",
"Tumour",
"γδ T cell"
] | 0 | 10.1002/eji.202451074 | [
"Schamel",
"Zintchenko",
"Nguyen",
"Fehse",
"Briquez",
"Minguet"
] | [
"Signaling Research Centres BIOSS and CIBSS; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.\nDepartment of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.\nCentre for Chronic Immunodeficiency (CCI), Faculty of Medicine, University Clinics Freiburg, Freiburg, Germany.",
"Signaling Research Centres BIOSS and CIBSS; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.\nDepartment of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.",
"Signaling Research Centres BIOSS and CIBSS; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.\nDepartment of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.\nSpemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany.",
"Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, and Hamburg Centre for Translational Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.\nHamburg Centre for Translational Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.",
"Department of General and Visceral Surgery, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany.",
"Signaling Research Centres BIOSS and CIBSS; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.\nDepartment of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.\nCentre for Chronic Immunodeficiency (CCI), Faculty of Medicine, University Clinics Freiburg, Freiburg, Germany."
] | [
"39192467"
] | [] | 8.68854 | 4.535753 |
39192433 | 565 | [Research Progress on the Influence of Blood Tumor Microen-vironment on the Efficacy and the Adverse Reactions of CAR-T Cell Immunotherapy--Review]. | The application of chimeric antigen receptor T cell (CAR-T) immunotherapy has ushered in a new era in cancer therapy, especially in the treatment of many kinds of refractory malignant tumors. The curative effect is significant for refractory/recurrent hematologic malignancies, such as acute leukemia, lymphoma, and multiple myeloma (MM). Tumor microenvironment (TME) is closely related to the efficacy and adverse reactions of CAR-T therapy. TME not only affects the activity of CAR-T cells, reduces their anti-tumor ability, but also directly involved in the occurrence and development of CAR-T cell therapy-related adverse reactions, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Therefore, a deeper understanding of the role of blood TME in the process of CAR-T immunotherapy and the occurrence and development of adverse reactions is helpful for the application of CAR-T therapy in hematological malignancies. In this review, the influence of blood TME on the efficacy and adverse reactions of CAR-T immunotherapy was briefly summarized, aiming to provide evidence-based support for the clinical optimization of therapeutic regimen of refractory/recurrent hematologic malignancies.
血液肿瘤微环境对CAR-T免疫疗法疗效及其不良反应的影响的研究进展.
嵌合抗原受体T细胞（CAR-T）免疫疗法的应用开创了肿瘤治疗的新时代，特别是在多种难治性恶性肿瘤的治疗中取得空前成功，对于难治/复发血液系统恶性肿瘤如急性白血病、淋巴瘤、多发性骨髓瘤（MM）等更是效果显著。肿瘤微环境（TME）与CAR-T疗法的疗效及不良反应关系密切，不仅影响CAR-T细胞的活性，降低其抗肿瘤能力，甚至直接参与CAR-T疗法相关不良反应如细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）的发生发展。因此，深入了解血液TME在CAR-T疗法治疗过程及不良反应中的作用，有助于拓展CAR-T疗法在血液系统恶性肿瘤中的应用。本文主要围绕血液TME对CAR-T疗法疗效和不良反应的影响进行综述，期望为临床优化难治/复发性血液系统恶性肿瘤的治疗方案提供循证依据。. | [
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] | 2024-08-28 | 1 | 39192433 | [
"adverse reactions",
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"blood TME",
"cancer therapy",
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"cytokine release syndrome",
"immunotherapy",
"hematological malignancies",
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"-T免疫疗法疗效及其不良反应的影响的研究进展",
"acute leukemia",
"CAR-T therapy",
"many kinds",
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"T免疫疗法疗效及其不良反应的影响的研究进展",
"lymphoma",
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"their anti-tumor ability",
"evidence-based support",
"血液肿瘤微环境对CAR"
] | [
"tumor microenvironment; chimeric antigen receptor T cells; immunotherapy; hematologic malignancies"
] | 0 | 10.19746/j.cnki.issn.1009-2137.2024.04.048 | [
"Liao",
"Lai",
"Li"
] | [
"Department of Hematology, Key Laboratory of Hematology, The Second Affiliated Hospital of Nanchang University.Nanchang 330006, Jiangxi Province, China.\nMedical College of Nanchang University, Nanchang 330006, Jiangxi Province, China.",
"Department of Hematology, Key Laboratory of Hematology, The Second Affiliated Hospital of Nanchang University.Nanchang 330006, Jiangxi Province, China.\nMedical College of Nanchang University, Nanchang 330006, Jiangxi Province, China.",
"Department of Hematology, Key Laboratory of Hematology, The Second Affiliated Hospital of Nanchang University.Nanchang 330006, Jiangxi Province, China.E-mail: [email protected]."
] | [
"39192433"
] | [] | 9.73294 | 4.839107 |
39192036 | 566 | Third-generation anti-CD19 CAR T cells for relapsed/refractory chronic lymphocytic leukemia: a phase 1/2 study. | Third-generation chimeric antigen receptor T cells (CARTs) for relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL) may improve efficacy compared to second-generation CARTs due to their enhanced CAR design. We performed the first phase 1/2 investigator-initiated trial evaluating escalating doses of third-generation CARTs (HD-CAR-1) targeting CD19 in patients with r/r CLL and B-cell lymphoma. CLL eligibility criteria were failure to two therapy lines including at least one pathway inhibitor and/or allogeneic hematopoietic cell transplantation. Nine heavily pretreated patients received HD-CAR-1 at dose levels ranging from 1 × 10 | [
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] | [] | 0 | 10.1038/s41375-024-02392-7 | [
"Derigs",
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] | [
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany. [email protected].",
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.",
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.",
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.",
"Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.\nBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.\nDepartment of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Berlin, Germany.",
"Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.\nBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.\nDepartment of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Berlin, Germany.\nGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)/National Center for Tumor Diseases (NCT), Heidelberg, Germany.\nHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.\nPrecision Healthcare University Research Institute, Queen Mary University of London, London, UK.",
"Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.\nBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.\nDepartment of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Berlin, Germany.",
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.",
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.",
"Department of Internal Medicine II, University Hospital Schleswig-Holstein, Kiel, Germany.",
"Department of Internal Medicine V, Klinikum Darmstadt, Darmstadt, Germany.",
"Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany.",
"Onkologie in Ettlingen, Ettlingen, Germany.",
"Department of Internal Medicine IV, University Hospital Giessen, Giessen, Germany.",
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.",
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.",
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.\nGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)/National Center for Tumor Diseases (NCT), Heidelberg, Germany.",
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.\nGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)/National Center for Tumor Diseases (NCT), Heidelberg, Germany.",
"Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.\nGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)/National Center for Tumor Diseases (NCT), Heidelberg, Germany."
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39191245 | 567 | Understanding the role of B cells in CAR T-cell therapy in leukemia through a mathematical model. | Chimeric antigen receptor T (CAR T) cell therapy has been proven to be successful against a variety of leukemias and lymphomas. This paper undertakes an analytical and numerical study of a mathematical model describing the competition of CAR T, leukemia, tumor, and B cells. Considering its significance in sustaining anti-CD19 CAR T-cell stimulation, a B-cell source term is integrated into the model. Through stability and bifurcation analyses, the potential for tumor eradication, contingent on the continuous influx of B cells, has been revealed, showing a transcritical bifurcation at a critical B-cell input. Additionally, an almost heteroclinic cycle between equilibrium points is identified, providing a theoretical basis for understanding disease relapse. Analyzing the oscillatory behavior of the system, the time-dependent dynamics of CAR T cells and leukemic cells can be approximated, shedding light on the impact of initial tumor burden on therapeutic outcomes. In conclusion, the study provides insights into CAR T-cell therapy dynamics for acute lymphoblastic leukemias, offering a theoretical foundation for clinical observations and suggesting avenues for future immunotherapy modeling research. | [
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] | 2024-08-28 | 1 | 39191245 | [
"B cells",
"CAR T cells",
"cell therapy",
"leukemic cells",
"CAR T",
"CAR T-cell therapy dynamics",
"initial tumor burden",
"Chimeric antigen receptor T",
"tumor eradication",
"acute lymphoblastic leukemias",
"anti-CD19 CAR T-cell stimulation",
"future immunotherapy modeling research",
"tumor",
"leukemia",
"leukemias",
"clinical observations",
"equilibrium points",
"a B-cell source term",
"a critical B-cell input",
"disease relapse",
"therapeutic outcomes",
"avenues",
"light",
"insights",
"a theoretical basis",
"stability and bifurcation analyses",
"a theoretical foundation",
"a mathematical model",
"a transcritical bifurcation",
"conclusion"
] | [] | 0 | 10.1063/5.0206341 | [
"Serrano",
"Barrio",
"Martínez-Rubio",
"Belmonte-Beitia",
"Pérez-García"
] | [
"IUMA, CoDy and Department of Applied Mathematics, Universidad de Zaragoza, Zaragoza 50009, Spain.",
"IUMA, CoDy and Department of Applied Mathematics, Universidad de Zaragoza, Zaragoza 50009, Spain.",
"Department of Mathematics, Universidad de Cádiz, Puerto Real, Cádiz 11510, Spain.\nBiomedical Research and Innovation Institute of Cádiz (INiBICA), Hospital Universitario Puerta del Mar, Cádiz 11002, Spain.",
"Mathematical Oncology Laboratory (MOLAB), Departament of Mathematics, Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Universidad de Castilla-La Mancha, Ciudad Real 13071, Spain.",
"Mathematical Oncology Laboratory (MOLAB), Departament of Mathematics, Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Universidad de Castilla-La Mancha, Ciudad Real 13071, Spain."
] | [
"39191245"
] | [] | 7.733964 | 4.742003 |
39190688 | 568 | Manufacturing CD20/CD19-targeted iCasp9 regulatable CAR-TSCM cells using a Quantum pBac-based CAR-T engineering system. | CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies. | [
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10.1200/JCO.2015.64.5929 | [
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39189923 | 569 | CAR T Cells Engineered to Secrete IFNκ Induce Tumor Ferroptosis via an IFNAR/STAT1/ACSL4 Axis. | Ferroptosis is an iron-dependent form of cell death that influences cancer immunity. Therapeutic modulation of ferroptosis is considered a potential strategy to enhance the efficacy of other cancer therapies, including immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy. In this study, we demonstrated that IFNκ influenced the induction of ferroptosis. IFNκ could enhance the sensitivity of tumor cells to ferroptosis induced by the small molecule compound erastin and the polyunsaturated fatty acid arachidonic acid. Mechanistically, IFNκ in combination with arachidonic acid induced immunogenic tumor ferroptosis via an IFNAR/STAT1/ACSL4 axis. Moreover, CAR T cells engineered to express IFNκ showed increased antitumor efficiency against H460 cells (antigen positive) and H322 cells (antigen-negative) both in vitro and in vivo. We conclude that IFNκ is a potential cytokine that could be harnessed to enhance the antitumor function of CAR T cells by inducing tumor ferroptosis. | [
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] | 2024-08-27 | 43 | 39189923 | [
"tumor cells",
"CAR T cells",
"H460 cells",
"cell death",
"immunogenic tumor ferroptosis",
"tumor ferroptosis",
"IFNκ",
"other cancer therapies",
"Ferroptosis",
"ferroptosis",
"arachidonic acid",
"chimeric antigen receptor",
"cancer immunity",
"antitumor efficiency",
"the polyunsaturated fatty acid arachidonic acid",
"Therapeutic modulation",
"immunotherapies",
"H460",
"the small molecule compound erastin",
"(CAR) T-cell therapy",
"H322",
"combination",
"a potential cytokine",
"a potential strategy",
"vivo",
"the antitumor function",
"IFNAR/STAT1/ACSL4",
"an iron-dependent form",
"an IFNAR/STAT1/ACSL4 axis",
"the efficacy"
] | [] | 0 | 10.1158/2326-6066.CIR-24-0130 | [
"Gao",
"Liu",
"Huang",
"Wang",
"Zhao",
"Cui",
"Peng",
"Li",
"Zhang"
] | [
"Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.\nSchool of Life Sciences, Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.\nSchool of Life Sciences, Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.\nTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.",
"Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.\nSchool of Public Health, Zhengzhou University, Zhengzhou, China.\nSchool of Life Sciences, Zhengzhou University, Zhengzhou, China.\nState Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China.\nTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China."
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39187850 | 570 | Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy. | In many hematologic malignancies, the adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated notable success; nevertheless, further improvements are necessary to optimize treatment efficacy. Current CAR-T therapies are particularly discouraging for solid tumor treatment. The immunosuppressive microenvironment of tumors affects CAR-T cells, limiting the treatment's effectiveness and safety. Therefore, enhancing CAR-T cell infiltration capacity and resolving the immunosuppressive responses within the tumor microenvironment could boost the anti-tumor effect. Specific strategies include structurally altering CAR-T cells combined with targeted therapy, radiotherapy, or chemotherapy. Overall, monitoring the tumor microenvironment and the status of CAR-T cells is beneficial in further investigating the viability of such strategies and advancing CAR-T cell therapy. | [
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10.1002/adma.202211509 | [
"Xia",
"Yang",
"Lu",
"Liu",
"Wang",
"Du",
"Li",
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"Wu"
] | [
"The Second Clinical Medical School, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.",
"The Second Clinical Medical School, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.",
"The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.\nForesea Life Insurance Guangzhou General Hospital, Guangzhou, 511300, China.",
"Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.",
"Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.",
"Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.",
"Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China. [email protected].",
"New York College of Traditional Chinese Medicine, Mineola, NY, 11501, USA. [email protected].",
"Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China. [email protected]."
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] | 2024-08-27 | 1 | 39187161 | [
"several safety expansion cohorts",
"Most patients",
"Patients",
"patients",
"ZUMA-1 Cohort",
"CRS",
"conditioning chemotherapy",
"an autologous anti-CD19 chimeric antigen receptor",
"anticonvulsant levetiracetam",
"neurologic events",
"Cohort",
"potential approaches",
"LBCL",
"an exploratory safety cohort",
"Axicabtagene ciloleucel",
"CAR T-cell-related toxicities",
"CAR) T-cell therapy",
"IL-6",
"prophylaxis",
"R/R LBCL",
"NEs",
"axi-cel experience cytokine release syndrome",
"the IL-6 receptor-blocking antibody tocilizumab",
"axi-cel",
"relapsed/refractory (R/R) large B-cell lymphoma",
"the pivotal ZUMA-1 trial",
"a single infusion",
"(CRS",
"Cohort 3",
"the use"
] | [
"Axi-cel",
"CAR T-cell therapy",
"LBCL"
] | 0 | 10.1016/j.jtct.2024.08.018 | [
"Locke",
"Neelapu",
"Bartlett",
"Lekakis",
"Jacobson",
"Braunschweig",
"Oluwole",
"Siddiqi",
"Lin",
"Timmerman",
"Kersten",
"Zheng",
"Zhang",
"Nater",
"Shen",
"Miao",
"Kim",
"Miklos"
] | [
"Moffitt Cancer Center, Tampa, Florida. Electronic address: [email protected].",
"M.D. Anderson Cancer Center, Houston, Texas.",
"Washington University School of Medicine, St. Louis, Missouri.",
"University of Miami Health System, Sylvester Comprehensive Cancer Center, Miami, Florida.",
"Dana-Farber Cancer Institute, Boston, Massachusetts.",
"Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.",
"Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.",
"City of Hope National Medical Center, Duarte, California.",
"Mayo Clinic, Rochester, Minnesota.",
"UCLA David Geffen School of Medicine, Los Angeles, California.",
"Amsterdam UMC, University of Amsterdam, Amsterdam, Cancer Center Amsterdam, Netherlands, on behalf of HOVON/LLPC.",
"Kite, a Gilead Company, Santa Monica, California.",
"Kite, a Gilead Company, Santa Monica, California.",
"Kite, a Gilead Company, Santa Monica, California.",
"Kite, a Gilead Company, Santa Monica, California.",
"Kite, a Gilead Company, Santa Monica, California.",
"Kite, a Gilead Company, Santa Monica, California.",
"Stanford University School of Medicine, Stanford, California."
] | [
"39187161"
] | [] | 5.764956 | 5.030758 |
39186002 | 572 | Activation of Cell-Intrinsic Signaling in CAR-T Cells via a Chimeric IL7R Domain. | Chimeric antigen receptor (CAR) T cells can effectively treat leukemias, but sustained antitumor responses can be hindered by a lack of CAR T-cell persistence. Cytotoxic effector T cells are short-lived, and establishment of CAR-T cells with memory to ensure immune surveillance is important. Memory T cells depend on cytokine support, with IL7 activation of the IL7 receptor (IL7R) being critical. However, IL7R surface expression is negatively regulated by exposure to IL7. We aimed to support CAR T-cell persistence by equipping CAR-T cells with a sustained IL7Rα signal. We engineered T cells to constitutively secrete IL7 or to express an anti-acute myeloid leukemia-targeted IL7Rα-chimeric cytokine receptor (CCR) and characterized the phenotype of these cell types. Canonical downstream signaling was activated in CCR-T cells with IL7R activation. When coexpressed with a cytotoxic CAR, functionality of both the CCR and CAR was maintained. We designed hybrid CAR-CCR and noted membrane proximity of the intracellular domains as vital for signaling. These data show cell-intrinsic cytokine support with canonical signaling, and functionality can be provided via expression of an IL7Rα domain whether independently expressed or incorporated into a cytotoxic CAR for use in anticancer therapy.
To improve the phenotype of tumor-directed T-cell therapy, we show that provision of cell-intrinsic IL7R-mediated signaling is preferable to activation of cells with exogenous IL7. We engineer this signaling via independent receptor engineering and incorporation into a CAR and validate maintained antigen-specific cytotoxic activity. | [
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] | 2024-08-26 | 62 | 39186002 | [
"T cells",
"Memory T cells",
"Cytotoxic effector T cells",
"cells",
"IL7 activation",
"CCR-T cells",
"CAR-T cells",
"CAR T-cell persistence",
"CAR",
"independent receptor engineering",
"cell-intrinsic cytokine support",
"exogenous IL7",
"IL7",
"CCR",
"IL7R activation",
"canonical signaling",
"tumor-directed T-cell therapy",
"noted membrane proximity",
"these cell types",
"IL7Rα",
"cytokine support",
"cell-intrinsic IL7R-mediated signaling",
"hybrid CAR-CCR",
"activation",
"antitumor responses",
"leukemias",
"anticancer therapy",
"maintained antigen-specific cytotoxic activity",
"immune surveillance",
"expression"
] | [] | 0 | 10.1158/2767-9764.CRC-24-0286 | [
"Vorri",
"Holl",
"Leeming",
"Apostolova",
"Marple",
"Ravich",
"Canbaz",
"Rahnama",
"Choe",
"Modi",
"Fearnow",
"Walsh",
"Pearce",
"Varadhan",
"Bonifant"
] | [
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, Australia.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.\nBloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.\nDivision of Hematology, University Hospital Basel, Basel, Switzerland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.\nDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.\nDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.\nBloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.\nBloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.\nDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland."
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39184661 | 573 | Current Strategies to Improve Chimeric Antigen Receptor T (CAR-T) Cell Persistence. | Chimeric antigen receptor T (CAR-T) cell therapy has transformed the field of immunology by redirecting T lymphocytes toward tumor antigens. Despite successes in attaining high remission rates as high as 90%, the performance of CAR therapy is limited by the survival of T cells. T cell persistence is crucial as it sustains immune response against malignancies, playing a critical role in cancer treatment outcomes. This review explores various approaches to improve CAR-T cell persistence, focusing on the choice between autologous and allogeneic cell sources, optimization of culture conditions for T cell subsets, metabolite adjustments to modify T cell metabolism, the use of oncolytic viruses (OVs), and advancements in CAR design. Autologous CAR-T cells generally exhibit longer persistence but are less accessible and cost-effective than their allogeneic counterparts. Optimizing culture conditions by promoting T | [
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39183354 | 574 | FGFR4-specific CAR-T cells with inducible caspase-9 suicide gene as an approach to treat rhabdomyosarcoma. | Metastatic rhabdomyosarcoma is associated with poor survival and unsatisfactory treatment outcomes. Therefore, new immunotherapeutic methods are urgently required. Fibroblast growth factor receptor 4 (FGFR4), a new therapeutic target for rhabdomyosarcoma, plays a crucial role in its onset and development. This study aimed to generate FGFR4 single-chain variable fragment-based chimeric antigen receptor (CAR) T cells without causing evident toxicity and incorporating an inducible caspase-9 (iCasp9) suicide gene system to enhance their safety. FGFR4 antigen expression was evaluated in normal murine tissues, normal human tissues, and specimens from patients with rhabdomyosarcoma. Combined with a 4-1BB co-stimulatory domain, a CD3ζ signaling domain, and an iCasp9 suicide gene, CAR-T cells with an FGFR4-specific single-chain variable fragment were developed. The specific cytotoxic effects, T-cell proliferation, cytokine secretion, apoptosis induction by chemical dimerization (AP20187), and toxicity of FGFR4 CAR-T cells were investigated in vitro and in vivo. FGFR4 CAR-T cells generated a variety of immune-promoting cytokines, including tumor necrosis factor α, interleukin 2, and interferon γ, and displayed effective cytotoxic activity against FGFR4-overexpressing rhabdomyosarcoma cells in vitro. FGFR4 CAR-T cells were relatively effective against FGFR4-overexpressing rhabdomyosarcoma, with tumor regression and poor survival in a subcutaneous xenograft model. The iCasp9 gene was incorporated into FGFR4 CAR-T cells and it was demonstrated that effective and reliable suicide gene activity depends on the administration of AP20187. By making use of the cross-reaction of FGFR4 CAR-T cells with murine FGFR4 in a syngeneic tumor model, this study found that FGFR4 CAR-T cells could regulate the growth of tumors without evident toxicity. Our study demonstrates that FGFR4 is a prospective target for CAR-T cell therapy in rhabdomyosarcoma without serious on-target off-tumor toxicity. FGFR4 CAR-T cells with the iCasp9 suicide gene system as a safety switch to limit toxicity may broaden the clinical applications of cellular therapy. | [
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] | 2024-08-26 | 37 | 39183354 | [
"T cells",
"FGFR4",
"murine FGFR4",
"FGFR4 CAR-T cells",
"FGFR4-overexpressing rhabdomyosarcoma cells",
"CAR-T cell therapy",
"FGFR4 CAR-T",
"tumor necrosis factor",
"tumor regression",
"Metastatic rhabdomyosarcoma",
"effective cytotoxic activity",
"evident toxicity",
"rhabdomyosarcoma",
"CAR-T cells",
"poor survival",
"T-cell proliferation",
"tumor",
"tumors",
"Fibroblast growth factor receptor",
"FGFR4-overexpressing rhabdomyosarcoma",
"normal murine tissues",
"normal human tissues",
"toxicity",
"effective and reliable suicide gene activity",
"FGFR4 single-chain variable fragment-based chimeric antigen receptor",
"the iCasp9 suicide gene system",
"FGFR4 antigen expression",
"iCasp9",
"new immunotherapeutic methods",
"cytokine secretion"
] | [] | 0 | 10.1038/s41417-024-00823-2 | [
"Xiao",
"Xu",
"Wang",
"Yu",
"Xu",
"Que",
"Zhao",
"Pan",
"Gao",
"Zhou",
"Zhang"
] | [
"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, China.\nMelanoma and Sarcoma Medical Oncology Unit, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.\nDepartment of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, 628 Zhenyuan Road, Guangming District, Shenzhen, Guangdong, 518107, China.",
"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, China.\nDepartment of Experimental Research, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, China.",
"Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Road, Guangzhou, Guangdong, 510080, China.",
"Department of Blood Transfusion, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330209, China.\nKey Laboratory of Jiangxi Province for Transfusion Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330209, China.",
"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, China.\nMelanoma and Sarcoma Medical Oncology Unit, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.",
"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, China.\nMelanoma and Sarcoma Medical Oncology Unit, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.",
"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, China.\nMelanoma and Sarcoma Medical Oncology Unit, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.",
"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, China.\nMelanoma and Sarcoma Medical Oncology Unit, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.",
"Department of Blood Transfusion, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330209, China.\nKey Laboratory of Jiangxi Province for Transfusion Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330209, China.",
"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, China. [email protected].\nDepartment of Experimental Research, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, China. [email protected].",
"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, China. [email protected].\nMelanoma and Sarcoma Medical Oncology Unit, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. [email protected]."
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] | [] | 8.729065 | 5.620981 |
39179404 | 575 | [Bioinformatic prediction and validation of cellular-mesenchymal epithelial transition(c-Met) as a target for chimeric antigen receptor T (CAR-T) cell therapy in the treatment of colorectal cancer]. | Objective To explore the potential of the cell surface receptor c-Met as an effective target for chimeric antigen receptor T-cell (CAR-T) therapy in colorectal cancer. Methods The bioinformatics was used to analyze the specific expression of c-Met in colorectal adenocarcinoma (COAD) and its clinical significance. c-Met protein expression was detected by immunohistochemistry in tumor tissues obtained from colorectal cancer patients. Flow cytometry was utilized to assess the expression of c-Met in the HCT116 human colorectal cancer cell line. Additionally, primary T cells isolated from human peripheral blood mononuclear cells (PBMCs) were transduced with a lentivirus to generate second-generation CAR-T cells targeting c-Met, followed by an observation of the inhibitory effects of these c-Met-targeted CAR-T cells on HCT116 cells. Results Immunohistochemistry and bioinformatics data both demonstrated that c-Met was over-expressed in COAD, with patients exhibiting relatively lower expression showing better prognosis. In normal colonic tissue, c-Met was either expressed at low levels or not expressed. Flow cytometry revealed high expression of c-Met in HCT116 cells as well. The c-Met-targeted CAR-T cells were capable of specifically recognizing and targeting antigen-expressing tumor cells. CAR-T cells proliferated specifically under antigenic stimulation, exerting cytotoxic effects on cancer cells and releasing cytokines interleukin 2 (IL-2) and interferon-gamma (IFN-γ), thereby demonstrating the biological functions. Conclusion c-Met may be a promising therapeutic target in COAD; c-Met-targeted CAR-T cells demonstrate inhibitory effects on colorectal cancer cells in vitro. | [
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] | 2024-08-24 | 1 | 39179404 | [
"colorectal cancer cells",
"cancer cells",
"primary T cells",
"human peripheral blood mononuclear cells",
"Met",
"colorectal cancer patients",
"colorectal cancer",
"high expression",
"Met protein expression",
"the HCT116 human colorectal cancer cell line",
"colorectal adenocarcinoma",
"antigen-expressing tumor cells",
"inhibitory effects",
"tumor tissues",
"cytotoxic effects",
"CAR-T cells",
"the cell surface receptor",
"c-Met",
"normal colonic tissue",
"COAD",
"Flow cytometry",
"second-generation CAR-T cells",
"Results Immunohistochemistry",
"low levels",
"antigenic stimulation",
"c-Met-targeted CAR-T cells",
"immunohistochemistry",
"HCT116 cells",
"chimeric antigen receptor T-cell (CAR-T) therapy",
"relatively lower expression"
] | [] | 0 | null | [
"Peng",
"Min",
"Long",
"Xie",
"Zhang",
"Li",
"Li"
] | [
"Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.",
"Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.",
"Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.",
"Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.",
"Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.",
"Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.",
"Department of Physiology, Bengbu Medical University, Bengbu 233030, China. *Corresponding author, E-mail: [email protected]."
] | [
"39179404"
] | [] | 10.389989 | 5.443823 |
39178136 | 576 | Novel CAR-T Cells Specifically Targeting SIA-CIgG Demonstrate Effective Antitumor Efficacy in Bladder Cancer. | Chimeric Antigen Receptor (CAR) T-cell therapy is a promising cancer treatment method. However, its application in bladder cancer (BC) remains limited, partially because of the absence of appropriate target molecules. Sialylated cancer-derived IgG (SIA-CIgG) is highly expressed in BC and is closely associated with malignant biological behavior. However, its potential as a target for CAR-T cell therapy to treat BC is yet to be established. Here, it is found that SIA-CIgG is highly expressed in most BC samples but displayed limited expression in normal tissues. CAR-T cells specifically targeting SIA-CIgG can effectively lyse BC cells and the cytotoxicity depends on SIA-CIgG expression. Furthermore, SIA-CIgG CAR-T cells demonstrate milder tumor cell lysis and enhanced persistence compared with human epidermal growth factor receptor 2 (HER2) CAR-T cells, which have undergone extensive clinical trials. After repeated tumor antigen challenges, SIA-CIgG CAR-T cells display substantial alterations in both the transcriptome and chromatin accessibility. When combining SIA-CIgG CAR-T cell therapy with FDA-approved drugs to treat BC, the histone deacetylase inhibitor (HDACi), vorinostat, is found to enhance the ablility of CAR-T cells for tumor cell lysis. Therefore, the combination of SIA-CIgG CAR-T cells and vorinostat is promising for BC treatment. | [
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] | 2024-08-23 | 58 | 39178136 | [
"BC cells",
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"normal tissues",
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] | [
"CAR‐T cell therapy",
"SIA‐CIgG",
"bladder cancer",
"combination therapy",
"vorinostat"
] | 0 | 10.1002/advs.202400156 | [
"Ding",
"Lin",
"Qin",
"Fu",
"Du",
"Qiu",
"Wei",
"Xu"
] | [
"Department of Urology, Peking University People's Hospital, Beijing, 100044, China.",
"Department of Urology, Peking University People's Hospital, Beijing, 100044, China.",
"Department of Urology, Peking University People's Hospital, Beijing, 100044, China.",
"Center for Cell and Gene Circuit Design, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.",
"Department of Urology, Peking University People's Hospital, Beijing, 100044, China.",
"Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.",
"Center for Cell and Gene Circuit Design, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.",
"Department of Urology, Peking University People's Hospital, Beijing, 100044, China."
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39175472 | 577 | Chimeric antigen receptor T-cells: a review on current status and future directions for relapsed/refractory multiple myeloma. | Although multiple myeloma is an incurable disease, the past decade has witnessed significant improvement in patient outcomes. This was brought about by the development of T-cell redirection therapies such as chimeric antigen receptor (CAR) T-cells, which can leverage the natural ability of the immune system to fight myeloma cells. The approval of the B-cell maturation antigen (BCMA)-directed CAR T, idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel) has resulted in a paradigm shift in the treatment of relapsed/refractory multiple myeloma. Overall response rates ranging from 73 to 97% are currently achievable. However, the limitations of KarMMa-1 and CARTITUDE-1 studies spurred the generation of real-world data to provide some insights into the effectiveness of ide-cel and cilta-cel among patients who were excluded from clinical trials, particularly those who received prior BCMA-targeted or other T-cell redirection therapies. Despite their unprecedented clinical efficacy in heavily pretreated patients, responses to CAR T remain non-durable. Although the underlying mechanisms of resistance to these agents haven't been fully elucidated, studies have suggested that resistance patterns could be multifaceted, implicating T-cell exhaustion and tumor intrinsic mechanisms such as BCMA target loss, upregulation of gamma-secretase, and others. Herein, we provide a succinct overview of the development of CAR T-cells, manufacturing process, and associated toxicities/complications. In this review, we also recapitulate the existing literature pertaining MM CAR-T as well as emerging data from some of the ongoing clinical trials designed to mitigate the shortcomings of these agents, and improve the clinical efficacy of CAR T, especially in the relapsed/refractory setting. | [
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10.1038/s41375-022-01531-2 | [
"Hamadeh",
"Friend",
"Mailankody",
"Atrash"
] | [
"Clinical Pharmacy Services, Pharmacy Department, Memorial Sloan Kettering Cancer Center, New York, NY, United States.",
"Plasma Cell Disorders Division, Department of Hematologic Oncology & Blood Disorders Levine Cancer Institute, Atrium Health, Charlotte, NC, United States.",
"Myeloma Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.",
"Plasma Cell Disorders Division, Department of Hematologic Oncology & Blood Disorders Levine Cancer Institute, Atrium Health, Charlotte, NC, United States."
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39175207 | 578 | iSECRETE: Integrating Microfluidics and DNA Proximity Amplification for Synchronous Single-Cell Activation and IFN-γ Secretion Profiling. | Cytokines, crucial in immune modulation, impact disease progression when their secretion is dysregulated. Existing methods for profiling cytokine secretion suffer from time-consuming and labor-intensive processes and often fail to capture the dynamic nature of immune responses. Here, iSECRETE, an integrated platform that enables synchronous cell activation, wash-free, and target-responsive protein detection for single-cell IFN-γ cytokine secretion analysis within 30 min at room temperature is presented. By incorporating a DNA proximity assay (DPA) into a multifunctional microfluidic system, one-pot homogenous cytokine signal amplification, with a limit of detection of ≈50 secreted molecules per cell is achieved. iSECRETE can robustly handle various sample types that are shown. Two distinct immune activation assay modalities are demonstrated on iSECRETE. Finally, the detection of single-cell IFN-γ secretion as an activation hallmark of chimeric antigen receptor T cells within 6 h of exposure to cancer targets is shown. iSECRETE represents the fastest single-cell sample-to-result cytokine secretion assay to date, providing a powerful tool for advancing the understanding of biological phenotypes, functions, and pathways under in vivo-like conditions. | [
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] | 2024-08-23 | 49 | 39175207 | [
"synchronous cell activation",
"cytokine secretion",
"chimeric antigen receptor T cells",
"cell",
"immune modulation",
"various sample types",
"single-cell IFN-γ cytokine secretion analysis",
"immune responses",
"Cytokines",
"impact disease progression",
"single-cell IFN-γ secretion",
"biological phenotypes",
"detection",
"cancer targets",
"IFN",
"room temperature",
"Two distinct immune activation",
"pathways",
"DPA",
"functions",
"Existing methods",
"iSECRETE",
"the fastest single-cell sample-to-result cytokine secretion",
"date",
"exposure",
"≈50",
"a multifunctional microfluidic system",
"one-pot homogenous cytokine signal amplification",
"their secretion",
"an activation hallmark"
] | [
"CAR T cells",
"cytokines",
"deterministic lateral displacement",
"immune profiling",
"microfluidics"
] | 0 | 10.1002/advs.202309920 | [
"Lu",
"Ang",
"Cheung",
"Quek",
"Sin",
"Lee",
"Lim",
"Yung",
"Birnbaum",
"Han",
"Cheow",
"Zeming"
] | [
"Critical Analytics for Manufacturing of Personalised Medicine IRG, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore.\nGraduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, 119077, Singapore.",
"Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.",
"Critical Analytics for Manufacturing of Personalised Medicine IRG, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore.",
"Critical Analytics for Manufacturing of Personalised Medicine IRG, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore.",
"Critical Analytics for Manufacturing of Personalised Medicine IRG, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore.",
"Critical Analytics for Manufacturing of Personalised Medicine IRG, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore.",
"National University Health System, National University Hospital, Singapore, 119228, Singapore.\nYong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.",
"Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.",
"Critical Analytics for Manufacturing of Personalised Medicine IRG, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore.\nDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.",
"Critical Analytics for Manufacturing of Personalised Medicine IRG, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore.\nDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.\nDepartment of Electrical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.",
"Critical Analytics for Manufacturing of Personalised Medicine IRG, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore.\nDepartment of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore.",
"Critical Analytics for Manufacturing of Personalised Medicine IRG, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore."
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] | [] | 8.801994 | 3.91844 |
39174908 | 579 | CD19 CAR T cells for B cell malignancies: a systematic review and meta-analysis focused on clinical impacts of CAR structural domains, manufacturing conditions, cellular product, doses, patient's age, and tumor types. | CD19-targeted chimeric antigen receptors (CAR) T cells are one of the most remarkable cellular therapies for managing B cell malignancies. However, long-term disease-free survival is still a challenge to overcome. Here, we evaluated the influence of different hinge, transmembrane (TM), and costimulatory CAR domains, as well as manufacturing conditions, cellular product type, doses, patient's age, and tumor types on the clinical outcomes of patients with B cell cancers treated with CD19 CAR T cells. The primary outcome was defined as the best complete response (BCR), and the secondary outcomes were the best objective response (BOR) and 12-month overall survival (OS). The covariates considered were the type of hinge, TM, and costimulatory domains in the CAR, CAR T cell manufacturing conditions, cell population transduced with the CAR, the number of CAR T cell infusions, amount of CAR T cells injected/Kg, CD19 CAR type (name), tumor type, and age. Fifty-six studies (3493 patients) were included in the systematic review and 46 (3421 patients) in the meta-analysis. The overall BCR rate was 56%, with 60% OS and 75% BOR. Younger patients displayed remarkably higher BCR prevalence without differences in OS. The presence of CD28 in the CAR's hinge, TM, and costimulatory domains improved all outcomes evaluated. Doses from one to 4.9 million cells/kg resulted in better clinical outcomes. Our data also suggest that regardless of whether patients have had high objective responses, they might have survival benefits from CD19 CAR T therapy. This meta-analysis is a critical hypothesis-generating instrument, capturing effects in the CD19 CAR T cells literature lacking randomized clinical trials and large observational studies. | [
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10.1038/s41571-021-00530-z | [
"Montagna",
"de Campos",
"Porto",
"da Silva",
"Suarez"
] | [
"Centro Universitário FMABC, Santo André, 09060-870, SP, Brazil.",
"Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, 09210-580, SP, Brazil.\nGraduate Program in Medicine - Hematology and Oncology, Federal University of São Paulo, São Paulo, 04023-062, SP, Brazil.",
"Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, 09210-580, SP, Brazil.",
"Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, 09210-580, SP, Brazil.",
"Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, 09210-580, SP, Brazil. [email protected].\nGraduate Program in Medicine - Hematology and Oncology, Federal University of São Paulo, São Paulo, 04023-062, SP, Brazil. [email protected]."
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39172238 | 580 | Management of chimeric antigen receptor T (CAR-T) cell-associated toxicities. | The use of chimeric antigen receptor T (CAR-T) cells is a significant therapeutic improvement increasing the prognosis for patients with a variety of hematological malignancies. However, this therapy has also sometimes life-threatening, complications. Therefore, knowledge of the treatment and management of these complications, especially in treatment centers and intensive care units, respectively, is of outstanding importance. This review provides recommendations for the diagnosis, management, and treatment of CAR-T cell-associated complications such as cytokine release syndrome, immune effector cell associated neurotoxicity syndrome, hematotoxicity, hypogammaglobulinemia, and CAR-T cell-induced pseudo-progression amongst others for physicians treating patients with CAR-T cell-associated complications and intensivists. | [
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] | 2024-08-22 | 70 | 39172238 | [
"immune effector cell associated neurotoxicity syndrome",
"treatment centers",
"cytokine release syndrome",
"intensive care units",
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"treatment",
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"patients",
"CAR-T cell-induced pseudo",
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"Department of Hematology and Oncology, Division of Stem Cell Transplantation and Cellular Immunotherapies, University Hospital Schleswig-Holstein Kiel, Kiel University, Arnold-Heller-Str. 3, 24106, Kiel, Germany.",
"Department of Hematology and Oncology, Division of Stem Cell Transplantation and Cellular Immunotherapies, University Hospital Schleswig-Holstein Kiel, Kiel University, Arnold-Heller-Str. 3, 24106, Kiel, Germany.",
"Department of Hematology and Oncology, Division of Stem Cell Transplantation and Cellular Immunotherapies, University Hospital Schleswig-Holstein Kiel, Kiel University, Arnold-Heller-Str. 3, 24106, Kiel, Germany.",
"Department of Hematology and Oncology, Division of Stem Cell Transplantation and Cellular Immunotherapies, University Hospital Schleswig-Holstein Kiel, Kiel University, Arnold-Heller-Str. 3, 24106, Kiel, Germany.",
"Department of Hematology and Oncology, Division of Stem Cell Transplantation and Cellular Immunotherapies, University Hospital Schleswig-Holstein Kiel, Kiel University, Arnold-Heller-Str. 3, 24106, Kiel, Germany.",
"Department of Hematology and Oncology, Division of Stem Cell Transplantation and Cellular Immunotherapies, University Hospital Schleswig-Holstein Kiel, Kiel University, Arnold-Heller-Str. 3, 24106, Kiel, Germany.",
"Department of Hematology and Oncology, Division of Stem Cell Transplantation and Cellular Immunotherapies, University Hospital Schleswig-Holstein Kiel, Kiel University, Arnold-Heller-Str. 3, 24106, Kiel, Germany.",
"Department of Hematology and Oncology, Division of Stem Cell Transplantation and Cellular Immunotherapies, University Hospital Schleswig-Holstein Kiel, Kiel University, Arnold-Heller-Str. 3, 24106, Kiel, Germany. [email protected]."
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39170618 | 581 | Traversing the bench to bedside journey for iNKT cell therapies. | Invariant natural killer T (iNKT) cells are immune cells that harness properties of both the innate and adaptive immune system and exert multiple functions critical for the control of various diseases. Prevention of graft-versus-host disease (GVHD) by iNKT cells has been demonstrated in mouse models and in correlative human studies in which high iNKT cell content in the donor graft is associated with reduced GVHD in the setting of allogeneic hematopoietic stem cell transplants. This suggests that approaches to increase the number of iNKT cells in the setting of an allogeneic transplant may reduce GVHD. iNKT cells can also induce cytolysis of tumor cells, and murine experiments demonstrate that activating iNKT cells | [
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"Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, United States.\nSiteman Cancer Center, Washington University in St. Louis, St. Louis, MO, United States."
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39169645 | 582 | Fibroblast activation protein constitutes a novel target of chimeric antigen receptor T-cell therapy in solid tumors. | With recent advances in tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has achieved unprecedented success in several hematologic tumors, significantly improving patient prognosis. However, in solid tumors, the efficacy of CAR-T cell therapy is limited because of high antigen uncertainty and the extremely restrictive tumor microenvironment (TME). This challenge has led to the exploration of new targets, among which fibroblast activation protein (FAP) has gained attention for its relatively stable and specific expression in the TME of various solid tumors, making it a potential new target for CAR-T cell therapy. This study comprehensively analyzed the biological characteristics of FAP and discussed its potential application in CAR-T cell therapy, including the theoretical basis, and preclinical and clinical research progress of targeting FAP with CAR-T cell therapy for solid tumor treatment. The challenges and future optimization directions of this treatment strategy were also explored, providing new perspectives and strategies for CAR-T cell therapy in solid tumors. | [
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] | 2024-08-22 | 80 | 39169645 | [
"solid tumor treatment",
"solid tumors",
"various solid tumors",
"several hematologic tumors",
"tumor immunotherapy",
"CAR-T cell therapy",
"new targets",
"new perspectives",
"FAP",
"high antigen uncertainty",
"fibroblast activation protein",
"future optimization directions",
"unprecedented success",
"strategies",
"TME",
"patient prognosis",
"recent advances",
"preclinical and clinical research progress",
"attention",
"CAR-T",
"the extremely restrictive tumor microenvironment",
"this treatment strategy",
"its potential application",
"the biological characteristics",
"the theoretical basis",
"its relatively stable and specific expression",
"the TME",
"The challenges",
"This challenge",
"the exploration"
] | [
"CAR‐T therapy",
"FAP",
"TME",
"solid tumors"
] | 0 | 10.1111/cas.16285 | [
"Meng",
"Hara",
"Miura",
"Ishii"
] | [
"Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Osaka, Japan.",
"Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Osaka, Japan.",
"Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan.\nDepartment of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan.",
"Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Osaka, Japan."
] | [
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] | [] | 9.000671 | 5.804666 |
39169624 | 583 | Targeting ROS-sensing Nrf2 potentiates anti-tumor immunity of intratumoral CD8 | Cytotoxic T lymphocytes (CTLs) play a crucial role in cancer rejection. However, CTLs encounter dysfunction and exhaustion in the immunosuppressive tumor microenvironment (TME). Although the reactive oxygen species (ROS)-rich TME attenuates CTL function, the underlying molecular mechanism remains poorly understood. The nuclear factor erythroid 2-related 2 (Nrf2) is the ROS-responsible factor implicated in increasing susceptibility to cancer progression. Therefore, we examined how Nrf2 is involved in anti-tumor responses of CD8 | [
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] | [
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10.1038/ng.3385 | [
"Jo",
"Shim",
"Jeong",
"Kim",
"Lee",
"Jeong",
"Kim",
"Im",
"Choi",
"Lee",
"Kim",
"Kim",
"Kim",
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] | [
"Department of Anatomy, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.",
"Department of Anatomy, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.",
"Department of Anatomy, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; PNU GRAND Convergence Medical Science Education Research Center, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.",
"Department of Anatomy, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; PNU GRAND Convergence Medical Science Education Research Center, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.",
"Department of Anatomy, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; PNU GRAND Convergence Medical Science Education Research Center, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.",
"Department of Anatomy and Cell Biology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.",
"Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.",
"NeoImmunetech, Co., Ltd., Pohang 37666, Republic of Korea.",
"NeoImmunetech, Co., Ltd., Pohang 37666, Republic of Korea.",
"NeoImmunetech, Inc., Rockville, MD 20850, USA.",
"Department of Anatomy, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.",
"Department of Pharmacology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.",
"School of Transdisciplinary Innovations and College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.",
"Department of Anatomy, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; PNU GRAND Convergence Medical Science Education Research Center, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea. Electronic address: [email protected]."
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39169622 | 584 | TALEN-edited allogeneic inducible dual CAR T cells enable effective targeting of solid tumors while mitigating off-tumor toxicity. | Adoptive cell therapy using chimeric antigen receptor (CAR) T cells has proven to be lifesaving for many cancer patients. However, its therapeutic efficacy has been limited in solid tumors. One key factor for this is cancer-associated fibroblasts (CAFs) that modulate the tumor microenvironment (TME) to inhibit T cell infiltration and induce "T cell dysfunction." Additionally, the sparsity of tumor-specific antigens (TSA) and expression of CAR-directed tumor-associated antigens (TAA) on normal tissues often results in "on-target off-tumor" cytotoxicity, raising safety concerns. Using TALEN-mediated gene editing, we present here an innovative CAR T cell engineering strategy to overcome these challenges. Our allogeneic "Smart CAR T cells" are designed to express a constitutive CAR, targeting FAP | [
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10.3389/fimmu.2021.640082 | [
"Dharani",
"Cho",
"Fernandez",
"Juillerat",
"Valton",
"Duchateau",
"Poirot",
"Das"
] | [
"Cellectis Inc, New York, NY 10016, USA.",
"Cellectis Inc, New York, NY 10016, USA.",
"Cellectis Inc, New York, NY 10016, USA.",
"Cellectis Inc, New York, NY 10016, USA.",
"Cellectis, 75013 Paris, France.",
"Cellectis, 75013 Paris, France.",
"Cellectis, 75013 Paris, France.",
"Cellectis Inc, New York, NY 10016, USA. Electronic address: [email protected]."
] | [
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] | [] | 9.178318 | 5.444608 |
39169164 | 585 | Novel immunotherapeutics against LGR5 to target multiple cancer types. | We have developed and validated a highly specific, versatile antibody to the extracellular domain of human LGR5 (α-LGR5). α-LGR5 detects LGR5 overexpression in >90% of colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pre-B-ALL tumour cells and was used to generate an Antibody-Drug Conjugate (α-LGR5-ADC), Bispecific T-cell Engager (α-LGR5-BiTE) and Chimeric Antigen Receptor (α-LGR5-CAR). α-LGR5-ADC was the most effective modality for targeting LGR5 | [
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] | 2024-08-22 | 55 | 39169164 | [
"LGR5 overexpression",
"human LGR5",
"LGR5",
"Chimeric Antigen Receptor",
"hepatocellular carcinoma",
"colorectal cancer",
"Bispecific T-cell Engager",
"CRC",
"HCC",
"Engager",
"Antibody-Drug Conjugate",
"the extracellular domain",
"α-LGR5-ADC",
"α-LGR5",
"α-LGR5-BiTE",
"α-LGR5-CAR",
"an Antibody-Drug Conjugate",
"a highly specific, versatile antibody",
"90%",
"the most effective modality",
">90%",
"ALL",
"We"
] | [
"ADC",
"BiTE",
"CAR",
"Cancer Immunotherapeutics",
"LGR5"
] | 0 | 10.1038/s44321-024-00121-2 | [
"Chen",
"Mueller",
"Stott",
"Kapeni",
"Rivers",
"Sauer",
"Beke",
"Walsh",
"Ashman",
"O'Brien",
"Rafati Fard",
"Ghodsinia",
"Li",
"Joud",
"Giger",
"Zlobec",
"Olan",
"Aitken",
"Hoare",
"Mair",
"Serrao",
"Brenton",
"Garcia-Gimenez",
"Richardson",
"Huntly",
"Spring",
"Skjoedt",
"Skjødt",
"de la Roche",
"de la Roche"
] | [
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.\nAstra Zeneca, Cambridge, UK.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge, CB2 1QW, UK.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge, CB2 1QW, UK.\nMRC-University of Glasgow Centre for Virus Research, Glasgow, UK.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, Yusuf Hamied Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK.\nBicycle Therapeutics, Cambridge, UK.",
"University of Cambridge, Yusuf Hamied Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK.\nCharles River Laboratories, Saffron Walden, UK.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge, CB2 1QW, UK.",
"University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge, CB2 1QW, UK.",
"University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge, CB2 1QW, UK.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, Department of Pathology, Tennis Court Road, Cambridge, CB2 1QP, UK.",
"Institute of Pathology, University of Bern, Murtenstrasse 31, CH-3008, Bern, Switzerland.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, MRC Toxicology Unit, Tennis Court Road, Cambridge, CB2 1QR, UK.\nDepartment of Histopathology, Cambridge University Hospitals, NHS Foundation Trust, Main Drive, Cambridge, CB2 0QQ, UK.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.",
"University of Cambridge, Department of Haematology, Puddicombe Way, Cambridge, CB2 0AW, UK.",
"University of Cambridge, Department of Haematology, Puddicombe Way, Cambridge, CB2 0AW, UK.",
"University of Cambridge, Department of Haematology, Puddicombe Way, Cambridge, CB2 0AW, UK.",
"University of Cambridge, Yusuf Hamied Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK.",
"Rigshospitalet-University Hospital Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.\nInstitute of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.\nNovo Nordisk, Måløv, Denmark.",
"University of Southern Denmark Campusvej 55, Odense M, DK-5230, Denmark.",
"University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge, CB2 1QW, UK. [email protected].",
"University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK. [email protected]."
] | [
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] | [] | 8.688391 | 5.962719 |
39168033 | 586 | Jump-starting chimeric antigen receptor-T cells to go the extra mile with nanotechnology. | Despite success in treating hematologic malignancies, chimeric antigen receptor-T cell (CAR-T) therapy still faces multiple challenges that have halted progress, especially against solid tumors. Recent advances in nanoscale engineeirng provide several avenues for overcoming these challenges, including more efficienct programming of CAR-Ts ex vivo, promoting immune responsiveness in the tumor microenvironment (TME) in vivo, and boosting CAR-T function in situ. Here, we summarize recent innovations that leverage nanotechnology to directly address the major obstacles that impede CAR-T therapy from reaching its full potential across various cancer types. We conclude with a commentary on the state of the field and how nanotechnology can shape the future of CAR-T and adoptive cell therapy in immuno-oncology. | [
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] | 2024-08-22 | 1 | 39168033 | [
"adoptive cell therapy",
"multiple challenges",
"more efficienct programming",
"CAR-T therapy",
"recent innovations",
"nanotechnology",
"hematologic malignancies",
"solid tumors",
"several avenues",
"Recent advances",
"various cancer types",
"nanoscale engineeirng",
"vivo",
"immune responsiveness",
"CAR-T function",
"CAR-T",
"CAR-Ts ex vivo",
"chimeric antigen receptor-T cell (CAR-T) therapy",
"TME",
"progress",
"success",
"the tumor microenvironment",
"situ",
"its full potential",
"the major obstacles",
"these challenges",
"immuno-oncology",
"the field",
"the future",
"the state"
] | [] | 0 | 10.1016/j.copbio.2024.103179 | [
"Chada",
"Wilson"
] | [
"Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA; Medical Scientist Training Program, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.",
"Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: [email protected]."
] | [
"39168033"
] | [] | 9.919864 | 3.561764 |
39166803 | 587 | Generation of Murine Chimeric Antigen Receptor-Modified T Cells for In Vivo Studies in Syngeneic Tumor Models. | CAR-T cell therapy has emerged as a potent and effective tool in the immunotherapy of refractory cancers. However, challenges exist in their clinical application, necessitating extensive preclinical research to optimize their function. Various preclinical in vitro and in vivo models have been proposed for such purpose; among which immunocompetent mouse models serve as an invaluable tool in studying host immune interactions within a more realistic simulation of the tumor milieu. We hereby describe a standardized protocol for the generation of high-titer γ-retroviral vectors through transfection of the HEK293T packaging cell line. The virus-containing supernatant is further concentrated using an inhouse concentrator solution, titrated, and applied to mouse T cells purified via a convenient and rapid method by nylon-wool columns. Using the method presented here, we were able to achieve high titer γ-retrovirus and highly pure mouse T cells with desirable CAR transduction efficiency. The mouse CAR T cells produced through this protocol demonstrate favorable CAR expression and viability, thus making them suitable for further in vitro/in vivo assays. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Production of γ-retroviral vectors from retrovirus-backbone plasmids Basic Protocol 2: Concentration of γ-retrovirus-containing supernatants Basic Protocol 3: Titration of concentrated γ-retrovirus Basic Protocol 4: Isolation and activation of mouse T cells Basic Protocol 5: Transduction of activated mouse T cells, assessment of CAR expression, and expansion of CAR T cells for further in vitro/in vivo studies Support Protocol: Surface staining of cells for flow cytometric assessment of CAR expression. | [
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] | 2024-08-21 | 1 | 39166803 | [
"mouse T cells",
"CAR T cells",
"T cells",
"activated mouse T cells",
"cells",
"Basic Protocol",
"immunocompetent mouse models",
"The mouse CAR T cells",
"γ-retroviral vectors",
"high titer γ",
"CAR-T cell therapy",
"favorable CAR expression",
"CAR expression",
"Support Protocol",
"the HEK293T packaging cell line",
"extensive preclinical research",
"concentrated γ-retrovirus Basic Protocol",
"-retrovirus and highly pure mouse T cells",
"host immune interactions",
"vivo models",
"flow cytometric assessment",
"CAR",
"desirable CAR transduction efficiency",
"high-titer γ-retroviral vectors",
"Wiley Periodicals",
"vivo studies",
"vivo assays",
"such purpose",
"assessment",
"refractory cancers"
] | [
"CAR T cell",
"adoptive cell therapy",
"cancer immunotherapy",
"mouse T cells",
"syngeneic models"
] | 0 | 10.1002/cpz1.1107 | [
"Hosseini",
"Akbari",
"Shahverdi",
"Hadjati",
"Faramarzi",
"Mirzaei",
"Yazdi"
] | [
"Department of Pharmaceutical Biotechnology, Tehran University of Medical Sciences, Tehran, Iran.",
"Department of Medical Immunology, Tehran University of Medical Sciences, Tehran, Iran.\nVilcek Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York.",
"Department of Pharmaceutical Biotechnology, Tehran University of Medical Sciences, Tehran, Iran.\nRecombinant Vaccine Research Center, Tehran University of Medical Sciences, Tehran, Iran.",
"Department of Medical Immunology, Tehran University of Medical Sciences, Tehran, Iran.",
"Department of Pharmaceutical Biotechnology, Tehran University of Medical Sciences, Tehran, Iran.",
"Department of Medical Immunology, Tehran University of Medical Sciences, Tehran, Iran.",
"Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran."
] | [
"39166803"
] | [] | 8.892913 | 2.938941 |
39164789 | 588 | Cardiac adverse events after Chimeric Antigen Receptor (CAR) T cell therapies: an updated systematic review and meta-analysis. | Chimeric antigen receptor (CAR) T-cell therapy is a new revolutionary method for treating refractory or relapsed hematologic malignancies, CAR T-cell therapy has been associated with cytokine release syndrome (CRS) and cardiotoxicity. We directed a systematic review and meta-analysis to determine the incidence and predictors of cardiovascular events (CVE) with CAR T-cell therapy.
We investigated PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for studies reporting cardiovascular outcomes in CAR-T cell recipients. The study protocol was listed in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42023478602). Twenty-three studies were included in this study.
The pooled incidence of CVE was 54% for arrhythmias, 30% for heart failure, 20% for cardiomyopathy, 10% for acute coronary syndrome, and 7% for cardiac arrest. Patients with CVE had a higher incidence of cytokine release syndrome grade ≥ 2 (RR 2.36, 95% CI 1.86-2.99). The incidence of cardiac mortality in our meta-analysis was 2% (95% CI: 1%-3%). Left ventricular ejection fraction decline was greater in the CVE group (-9.4% versus -1.5%, p < 0.001). Cardiac biomarkers like BNP, CRP, creatinine, and ferritin were also elevated.
CAR T-cell therapy commonly leads to cardiotoxicity, mediated by cytokine release syndrome. Vigilant monitoring and tailored treatments are crucial to mitigate these effects. Importantly, there's no significant difference in cardiac mortality between groups, suggesting insights for optimizing preventive interventions and reducing risks after CAR T-cell therapy. | [
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] | 0 | 10.1186/s40959-024-00252-y
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10.3389/fonc.2022.924208 | [
"Maleki",
"Esmaeili",
"Seighali",
"Shafiee",
"Namin",
"Zavareh",
"Khamene",
"Mohammadkhawajah",
"Nanna",
"Alizadeh-Asl",
"M Kwan",
"Hosseini"
] | [
"School of Medicine, Guilan University of Medical Sciences (GUMS), Rasht, Guilan Province, Iran.\nCardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.\nTehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, North Kargar Ave, Tehran, 1411713138, Iran.",
"Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.\nTehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, North Kargar Ave, Tehran, 1411713138, Iran.\nSchool of Medicine, Tehran University of Medical Sciences, Tehran, Iran.",
"Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.",
"Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.",
"Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.\nTehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, North Kargar Ave, Tehran, 1411713138, Iran.",
"Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.",
"School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.",
"School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.",
"Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA.",
"Professor of Cardiology Echocardiologist, Cardio-Oncologist Founder of Cardio-Oncology in Iran Cardio-Oncology Research Center Rajaie Cardiovascular Medical & Research Institute, Tehran, Iran.",
"Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, 06520, USA.",
"Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. [email protected].\nTehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, North Kargar Ave, Tehran, 1411713138, Iran. [email protected]."
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39164422 | 589 | Variability in morphology and immunohistochemistry of Crohn's disease-associated small bowel neoplasms: implications of Claudin 18 and Cadherin 17 expression for tumor-targeted immunotherapies. | Inflammatory bowel disease-associated colorectal carcinomas are known to have different morphology, immunoprofile, and genetic findings from sporadic colorectal carcinomas; however, little is known for Crohn's disease-associated small bowel neoplasms (CD-SBNs). Cadherin 17 is a useful biomarker of adenocarcinomas with intestinal phenotype and recently reported as an ideal target for chimeric antigen receptor T-cells (CAR-T) therapy for gastrointestinal carcinoma. Claudin 18 is a cell adhesion protein, and Claudin18 isoform 2 (CLDN18.2) is frequently expressed at high levels in gastric-type adenocarcinoma. Zolbetuximab, a targeted monoclonal antibody, has been developed for CLDN18.2-positive gastroesophageal adenocarcinoma. We examined a series of CD-SBNs for both Cadherin 17 and Claudin 18, and also hypothesized that expression of Claudin 18 was associated with gastric phenotype.
We performed histological and immunohistochemical examinations on 25 CD-SBNs. Most of adenocarcinomas showed tubular morphology as seen in gastric carcinomas, whereas a subset of dysplasia was morphologically similar to that of the large bowel. Cadherin17 and Claudin 18 expression was identified in 93% and 57% CD-associated adenocarcinomas respectively. In Cadherin 17-positive CD-SBNs, frequent MUC5AC, MUC6, and Claudin18 expression was identified (61%, 57%, and 57%, respectively). Claudin 18-positive CD-SBNs showed significantly more MUC5AC and MUC6 expression than Claudin 18-negative CD-SBNs (P = 0.005, < 0.001 respectively).
In CD-associated small bowel adenocarcinomas, Cadherin 17 expression was frequently retained and Claudin 18 was frequently co-expressed. Claudin 18 had a positive correlation with the expression of gastric mucins. These results suggest that CD-associated small bowel adenocarcinomas may be candidates for Cadherin 17- and Claudin 18-targeted immunotherapies. | [
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] | 2024-08-21 | 25 | 39164422 | [
"gastric carcinomas",
"Claudin18 expression",
"sporadic colorectal carcinomas",
"gastric phenotype",
"CD-associated small bowel adenocarcinomas",
"gastrointestinal carcinoma",
"Claudin",
"Inflammatory bowel disease-associated colorectal carcinomas",
"carcinomas",
"gastric mucins",
"adenocarcinomas",
"tubular morphology",
"different morphology",
"Cadherin",
"Claudin18 isoform",
"intestinal phenotype",
"CLDN18.2-positive gastroesophageal adenocarcinoma",
"57% CD-associated adenocarcinomas",
"CD-SBNs",
"CLDN18.2",
"high levels",
"Crohns disease-associated small bowel neoplasms",
"Claudin18",
"chimeric antigen receptor T-cells",
"gastric-type adenocarcinoma",
"Cadherin 17 expression",
"Cadherin 17-positive CD-SBNs",
"Claudin 18-positive CD-SBNs",
"Cadherin17 and Claudin 18 expression",
"significantly more MUC5AC and MUC6 expression"
] | [
"Claudin 18 and Cadherin 17",
"Crohn’s disease, small bowel",
"Inflammatory bowel disease-associated carcinoma, dysplasia"
] | 0 | 10.1007/s00428-024-03896-4 | [
"Iwaya",
"Kodama",
"Abe",
"Maeda",
"Nakajima",
"Uehara",
"Nishio",
"Yamana",
"Riddell",
"Ota"
] | [
"Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, Japan. [email protected].",
"Department of Pathology, Tokyo Yamate Medical Center, Tokyo, Japan.",
"Department of Pathology, Tokyo Yamate Medical Center, Tokyo, Japan.",
"Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, Japan.",
"Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, Japan.",
"Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.",
"Department of Coloproctology Center, Tokyo Yamate Medical Center, Tokyo, Japan.",
"Department of Coloproctology Center, Tokyo Yamate Medical Center, Tokyo, Japan.",
"Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.\nDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.",
"Department of Clinical Laboratory Sciences, School of Health Sciences, Shinshu University, Matsumoto, Japan."
] | [
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] | [] | 8.63092 | 6.26194 |
39164224 | 590 | CAR T-cell-mediated delivery of bispecific innate immune cell engagers for neuroblastoma. | Novel chimeric antigen receptor (CAR) T-cell approaches are needed to improve therapeutic efficacy in solid tumors. High-risk neuroblastoma is an aggressive pediatric solid tumor that expresses cell-surface GPC2 and GD2 with a tumor microenvironment infiltrated by CD16a-expressing innate immune cells. Here we engineer T-cells to express a GPC2-directed CAR and simultaneously secrete a bispecific innate immune cell engager (BiCE) targeting both GD2 and CD16a. In vitro, GPC2.CAR-GD2.BiCE T-cells induce GPC2-dependent cytotoxicity and secrete GD2.BiCE that promotes GD2-dependent activation of antitumor innate immunity. In vivo, GPC2.CAR-GD2.BiCE T-cells locally deliver GD2.BiCE and increase intratumor retention of NK-cells. In mice bearing neuroblastoma patient-derived xenografts and reconstituted with human CD16a-expressing immune cells, GD2.BiCEs enhance GPC2.CAR antitumor efficacy. A CAR.BiCE strategy should be considered for tumor histologies where antigen escape limits CAR efficacy, especially for solid tumors like neuroblastoma that are infiltrated by innate immune cells. | [
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] | 2024-08-21 | 86 | 39164224 | [
"innate immune cells",
"solid tumors",
"tumor histologies",
"CD16a-expressing innate immune cells",
"human CD16a-expressing immune cells",
"limits CAR efficacy",
"GPC2.CAR antitumor efficacy",
"a bispecific innate immune cell engager",
"Novel chimeric antigen receptor",
"therapeutic efficacy",
"cell-surface GPC2",
"T-cells",
"CD16a",
"an aggressive pediatric solid tumor",
"antigen",
"NK-cells",
"GD2.BiCE",
"CAR",
"intratumor retention",
"GPC2.CAR-GD2.BiCE T-cells",
"antitumor",
"neuroblastoma",
"GD2",
"CAR) T-cell approaches",
"neuroblastoma patient-derived xenografts",
"GPC2-dependent cytotoxicity",
"a tumor microenvironment",
"GD2-dependent activation",
"secrete",
"GD2.BiCEs"
] | [] | 0 | 10.1038/s41467-024-51337-2 | [
"Pascual-Pasto",
"McIntyre",
"Hines",
"Giudice",
"Garcia-Gerique",
"Hoffmann",
"Mishra",
"Matlaga",
"Lombardi",
"Shraim",
"Schürch",
"Yarmarkovich",
"Hofmann",
"Alikarami",
"Martinez",
"Tsang",
"Gil-de-Gómez",
"Spear",
"Bernt",
"Wolpaw",
"Dimitrov",
"Li",
"Bosse"
] | [
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, 19104, USA.\nCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.\nDepartment of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.\nDepartment of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.\nNew York University, Perlmutter Cancer Center, Grossman School of Medicine, New York, NY, 10016, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.\nDepartment of Molecular Biology, University of Cantabria School of Medicine, Santander, Cantabria, 39011, Spain.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.\nDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.\nDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.",
"Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.",
"Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.",
"Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. [email protected].\nDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA. [email protected]."
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] | [] | 9.804229 | 6.991446 |
39163531 | 591 | BTK inhibitors: moving the needle on the treatment of chronic lymphocytic leukemia. | Bruton's tyrosine kinaseinhibitors (BTKis) changed the trajectory of upfront and relapsed/refractory chronic lymphocytic leukemia (CLL) treatment. However, BTKis are plagued by a spectrum of toxicities. Zanubrutinib was developed to circumvent challenges with prolonged tolerability by increasing BTK selectivity and maximizing efficacy through pharmacokinetic/pharmacodynamic optimization. However, with the availability of ibrutinib, acalabrutinib, and zanubrutinib, limited data exists to guide sequencing of BTKi therapy in the relapsed/refractory setting.
We review the first head-to-head trial (ALPINE) of zanubrutinib versus ibrutinib for the treatment of relapsed/refractory CLL and compare zanubrutinib's clinical efficacy and toxicities, including in patients with del(17p) and/or
Zanubrutinibrepresents one of the new standards of care for relapsed/refractory CLL based on superior progression-free survival and response rates over ibrutinib. Whilezanubrutinib is associated with fewer cardiac toxicities, similar rates of neutropenia and hypertension are noted. Ongoing studies are pushing the envelope, utilizing targeted drug combinations and minimal residual disease markers as well as receptor tyrosine kinase-like orphan receptor 1 inhibitors, chimeric antigen receptor T-cells, and novel BTK degraders. However, zanubrutinibrepresents a strong contender in the arsenal of treatment options for relapsed/refractory CLL. | [
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"fewer cardiac toxicities",
"minimal residual disease markers",
"maximizing efficacy",
"targeted drug combinations",
"toxicities",
"BTK selectivity",
"treatment options",
"similar rates",
"novel BTK degraders",
"relapsed/refractory CLL",
"zanubrutinib",
"CLL",
"response rates",
"receptor tyrosine kinase-like orphan receptor",
"prolonged tolerability",
"ibrutinib",
"BTK",
"limited data",
"BTKi therapy",
"head",
"chimeric antigen receptor T-cells",
"BTKis",
"relapsed/refractory chronic lymphocytic leukemia (CLL) treatment",
"Ongoing studies",
"zanubrutinibs clinical efficacy",
"challenges",
"the relapsed/refractory setting",
"superior progression-free survival",
"neutropenia",
"care"
] | [
"ALPINE",
"BTK inhibitor",
"Bruton’s tyrosine kinase",
"chronic lymphocytic leukemia",
"zanubrutinib"
] | 0 | 10.1080/17474086.2024.2391097 | [
"Hatashima",
"Shadman"
] | [
"Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA.",
"Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA.\nDivision of Hematology and Oncology, University of Washington, Seattle, WA, USA."
] | [
"39163531"
] | [] | 6.146157 | 6.316615 |
39156126 | 592 | Strategies to overcome tumor microenvironment immunosuppressive effect on the functioning of CAR-T cells in high-grade glioma. | Despite significant progress in the treatment of some types of cancer, high-grade gliomas (HGGs) remain a significant clinical problem. In the case of glioblastoma (GBM), the most common solid tumor of the central nervous system in adults, the average survival time from diagnosis is only 15-18 months, despite the use of intensive multimodal therapy. Chimeric antigen receptor (CAR)-expressing T cells, which have already been approved by the Food and Drug Administration for use in the treatment of certain hematologic malignancies, are a new, promising therapeutic option. However, the efficacy of CAR-T cells in solid tumors is lower due to the immunosuppressive tumor microenvironment (TME). Reprogramming the immunosuppressive TME toward a pro-inflammatory phenotype therefore seems particularly important because it may allow for increasing the effectiveness of CAR-T cells in the therapy of solid tumors. The following literature review aims to present the results of preclinical studies showing the possibilities of improving the efficacy of CAR-T in the TME of GBM by reprogramming the TME toward a pro-inflammatory phenotype. It may be achievable thanks to the use of CAR-T in a synergistic therapy in combination with oncolytic viruses, radiotherapy, or epigenetic inhibitors, as well as by supporting CAR-T cells crossing of the blood-brain barrier, normalizing impaired angiogenesis in the TME, improving CAR-T effector functions by cytokine signaling or by blocking/knocking out T-cell inhibitors, and modulating the microRNA expression. The use of CAR-T cells modified in this way in synergistic therapy could lead to the longer survival of patients with HGG by inducing an endogenous anti-tumor response. | [
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] | 2024-08-19 | 80 | 39156126 | [
"T cells",
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] | [
"chimeric antigen receptor",
"glioblastoma",
"immunosuppressive tumor microenvironment"
] | 0 | 10.1177/17588359241266140 | [
"Zarychta",
"Kowalczyk",
"Marszołek",
"Zawitkowska",
"Lejman"
] | [
"Student Scientific Society of Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Lublin, Poland.",
"Student Scientific Society of Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Lublin, Poland.",
"Student Scientific Society of Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, Lublin, Poland.",
"Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Lublin, Poland.",
"Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, A. Racławickie 1, Lublin 20-093, Poland."
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39153835 | 593 | CD19-CAR T-cell therapy induces deep tissue depletion of B cells. | CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo.
Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs. Results were compared with lymph node biopsies from rituximab (RTX)-treated AID patients with absence of peripheral B cells. Conventional and immunohistochemistry staining were performed on lymph node tissue to assess architecture as well the number of B cells, follicular dendritic cells (FDCs), plasma cells, T cells and macrophages.
Sequential lymph node biopsies were analysed from five patients with AID before and after CD19-CAR T-cell therapy and from five patients with AID after RTX treatment. In addition, non-lymphoid organ biopsies (colon, kidney and gallbladder) from three additional patients with AID after CD19-CAR T-cell therapy were analysed. CD19
This study demonstrates complete B-cell depletion in secondary lymphoid tissues of patients with AIDs following CD19-CAR T-cell therapy combined with standard lymphodepleting therapy. | [
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] | 2024-08-18 | 1 | 39153835 | [
"B cells",
"peripheral B cells",
"T cells",
"plasma cells",
"follicular dendritic cells",
"lymph node biopsies",
"Sequential lymph node biopsies",
"lymph node tissue",
"node biopsies",
"non-lymphoid organ biopsies",
"patients",
"standard lymphodepleting therapy",
"secondary lymphoid tissues",
"AID",
"AIDs",
"CD19-CAR T-cell therapy",
"complete B-cell depletion",
"deep tissue depletion",
"Sequential ultrasound-guided inguinal lymph node biopsies",
"CAR) T-cell therapy",
"rituximab (RTX)-treated AID patients",
"such effect",
"CD19-targeting chimeric antigen receptor",
"autoimmune diseases",
"three additional patients",
"RTX treatment",
"colon",
"kidney",
"FDCs",
"gallbladder"
] | [
"Autoimmune Diseases",
"B-Lymphocytes",
"Rituximab",
"Ultrasonography"
] | 0 | 10.1136/ard-2024-226142 | [
"Tur",
"Eckstein",
"Velden",
"Rauber",
"Bergmann",
"Auth",
"Bucci",
"Corte",
"Hagen",
"Wirsching",
"Grieshaber-Bouyer",
"Reis",
"Kittan",
"Wacker",
"Rius Rigau",
"Ramming",
"D'Agostino",
"Hartmann",
"Müller",
"Mackensen",
"Bozec",
"Schett",
"Raimondo"
] | [
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.\nDivision of Rheumatology-Fondazione Policlinico Universitario A. Gemelli, IRCCS-Università Cattolica del Sacro Cuore, Roma, Lazio, Italy.",
"Institute of Pathology and Comprehensive Cancer Center EMN, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.",
"Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Division of Rheumatology-Fondazione Policlinico Universitario A. Gemelli, IRCCS-Università Cattolica del Sacro Cuore, Roma, Lazio, Italy.",
"Institute of Pathology and Comprehensive Cancer Center EMN, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.",
"Department of Medicine 5-Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Uniklinikum Erlangen, Erlangen, Bayern, Germany.",
"Department of Medicine 5-Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Uniklinikum Erlangen, Erlangen, Bayern, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany.\nDivision of Rheumatology-Fondazione Policlinico Universitario A. Gemelli, IRCCS-Università Cattolica del Sacro Cuore, Roma, Lazio, Italy.",
"Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany [email protected].\nDeutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany."
] | [
"39153835"
] | [] | 6.770589 | 5.279958 |
39152952 | 594 | Late-onset relapsing neurotoxicity after Brexucabtagene autoleucel associated with high chimeric antigen receptor T cells in cerebrospinal fluid. | Mounting evidence suggests that persistent cell expansion is the main driver for both efficacy and toxicity of chimeric antigen receptor (CAR) T-cell therapy. Hereby, we describe a case of delayed recurrent neurotoxicity associated with late CAR T-cells re-expansion.
A 44-year-old man suffering from mantle cell lymphoma received brexu-cel. After infusion, he developed grade 2 cytokine release syndrome. On day +11, grade 3 neurotoxicity was reported and high-dose methylprednisolone was started with a complete resolution of neurological manifestations. On day +30, he experienced a late-onset CAR T-cell toxicity associated with CAR T-cell re-expansion. The patient was treated with tocilizumab and dexamethasone, with resolution of symptoms. On day +58, he was readmitted for new onset of neurotoxicity. Notably, a new CAR T-cell expansion was observed, with an unexpectedly elevated cerebrospinal fluid/blood ratio. The patient was promptly treated with dexamethasone and then escalated to high-dose methylprednisolone and anakinra, with resolution of his neurologic condition noted.
CAR T-cell-related neurotoxicity usually has an early monophasic course. To our knowledge, this is the first case of late-onset, recurrent neurotoxicity. Moreover, an elevated level of cerebrospinal fluid CAR T cells was observed, which may suggest that the delayed neurotoxicity was primarily caused by the brain infiltration of CAR T cells rather than driven by cytokine-mediated neuroinflammation. | [
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] | 2024-08-17 | 1 | 39152952 | [
"cerebrospinal fluid CAR T cells",
"persistent cell expansion",
"CAR T cells",
"mantle cell lymphoma",
"delayed recurrent neurotoxicity",
"late CAR T-cells",
"neurotoxicity",
"CAR T-cell re",
"CAR T-cell-related neurotoxicity",
"new onset",
"a new CAR T-cell expansion",
"resolution",
"expansion",
"a late-onset CAR T-cell toxicity",
"chimeric antigen receptor",
"day +30",
"dexamethasone",
"high-dose methylprednisolone",
"(CAR) T-cell therapy",
"the delayed neurotoxicity",
"late-onset, recurrent neurotoxicity",
"toxicity",
"day",
"grade 2 cytokine release syndrome",
"neurological manifestations",
"re",
"Mounting evidence",
"mantle",
"-",
"tocilizumab"
] | [
"CAR T-cell",
"CAR T-cells re-expansion",
"late-onset neurotoxicity",
"mantle cell lymphoma"
] | 0 | 10.1016/j.jcyt.2024.07.015 | [
"De Philippis",
"Giacomel",
"Pensato",
"Pinton",
"Taurino",
"Mannina",
"Mariotti",
"Sarina",
"Marcheselli",
"Timofeeva",
"Capizzuto",
"Santoro",
"Bramanti"
] | [
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy. Electronic address: [email protected].",
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy.",
"Department of Biomedical Sciences, Humanitas University, Milan, Italy; IRCCS Humanitas Research Hospital, Milan, Italy.",
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy.",
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy.",
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy.",
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy.",
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy.",
"IRCCS Humanitas Research Hospital, Milan, Italy.",
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy.",
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy.",
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy.",
"IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy."
] | [
"39152952"
] | [] | 6.121756 | 4.592609 |
39152647 | 595 | Chimeric Antigen Receptor T-cell based cellular therapies for cancer: An introduction and Indian perspective. | Using one's own immune system for curing cancer has been an active field of research in cancer biology and therapeutics. One such opportunity in cellular immunotherapy is adoptive cell transfers. With the recent approval of CAR-T therapy as a cancer treatment, a whole new paradigm of cancer treatment has opened-up, with a ray of hope for relapsed/refractory cancer patients. Despite promising clinical outcomes, the therapy is in its early phase and remains out of reach for most patients due to its high cost and logistic challenges. In India, these therapies are unavailable and further confounded by the economic challenges and a large population. In this review, we discuss various aspects of T-cell immunotherapies with a special focus on CAR-T in the Indian scenario. We touch upon the basic scientific aspects, mechanism of action, manufacturing, clinical aspects and commercial aspects of the CAR-Tcell therapies and its future worldwide and in India. | [
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] | 2024-08-17 | 1 | 39152647 | [
"cancer treatment",
"clinical aspects",
"cancer biology",
"various aspects",
"commercial aspects",
"cancer",
"cellular immunotherapy",
"adoptive cell transfers",
"most patients",
"clinical outcomes",
"relapsed/refractory cancer patients",
"CAR-T therapy",
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"India",
"action",
"manufacturing",
"the CAR-Tcell therapies",
"Indian",
"CAR-T",
"the therapy",
"these therapies",
"a whole new paradigm",
"the economic challenges",
"therapeutics"
] | [] | 0 | 10.4103/ijc.ijc_433_21 | [
"Rathod",
"Sukumaran",
"Kedia",
"Kumar",
"Nair",
"Chandy",
"Gandikota",
"Radhakrishnan"
] | [
"Cell and Gene Therapy Division, Intas Pharmaceuticals, Ahmedabad, Gujarat, India.",
"Hematology Oncology and HCT, Tata Medical Center, Kolkata, West Bengal, India.",
"Cell and Gene Therapy Division, Intas Pharmaceuticals, Ahmedabad, Gujarat, India.",
"Hematology Oncology and HCT, Tata Medical Center, Kolkata, West Bengal, India.",
"Hematology Oncology and HCT, Tata Medical Center, Kolkata, West Bengal, India.",
"Hematology Oncology and HCT, Tata Medical Center, Kolkata, West Bengal, India.",
"Cell and Gene Therapy Division, Intas Pharmaceuticals, Ahmedabad, Gujarat, India.",
"Hematology Oncology and HCT, Tata Medical Center, Kolkata, West Bengal, India."
] | [
"39152647"
] | [] | 9.571819 | 3.779431 |
39151930 | 596 | NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors. | Antitumor effect of chimeric antigen receptor (CAR)-T cells against solid tumors is limited due to various factors, such as low infiltration rate, poor expansion capacity, and exhaustion of T cells within the tumor. NR4A transcription factors have been shown to play important roles in T-cell exhaustion in mice. However, the precise contribution of each NR4a factor to human T-cell differentiation remains to be clarified.
In this study, we deleted NR4A family factors,
Human NR4A-TKO CAR-T cells were resistant against exhaustion induced by repeated antigen stimulation in vitro, and maintained higher tumor-killing activity both in vitro and in vivo compared with control CAR-T cells. A comparison of the effectiveness of NR4A single, double, and TKOs demonstrated that triple KO was the most effective in avoiding exhaustion. Furthermore, a strong enhancement of antitumor effects by NR4A TKO was also observed in T cells from various donors including aged persons. Mechanistically, NR4A TKO CAR-T cells showed enhanced mitochondrial oxidative phosphorylation, therefore could persist for longer periods within the tumors.
NR4A factors regulate CAR-T cell persistence and stemness through mitochondrial gene expression, therefore NR4A is a highly promising target for the generation of superior CAR-T cells against solid tumors. | [
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"T cells",
"CAR)-T cells",
"NR4A transcription factors",
"NR4A TKO",
"various factors",
"NR4A family factors",
"NR4A TKO CAR-T cells",
"NR4A",
"solid tumors",
"control CAR-T cells",
"NR4A factors",
"superior CAR-T cells",
"CAR-T cell persistence",
"T-cell exhaustion",
"Human NR4A-TKO CAR-T cells",
"enhanced mitochondrial oxidative phosphorylation",
"mitochondrial gene expression",
"human T-cell differentiation",
"various donors",
"exhaustion",
"antitumor effects",
"repeated antigen stimulation",
"low infiltration rate",
"chimeric antigen receptor",
"poor expansion capacity",
"TKO",
"Antitumor effect",
"triple KO",
"important roles",
"higher tumor-killing activity"
] | [
"Adoptive cell therapy - ACT",
"Chimeric antigen receptor - CAR",
"Lung Cancer",
"Solid tumor",
"Stem cell"
] | 0 | 10.1136/jitc-2023-008665
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10.1038/s41590-020-0793-3 | [
"Nakagawara",
"Ando",
"Srirat",
"Mise-Omata",
"Hayakawa",
"Ito",
"Fukunaga",
"Yoshimura"
] | [
"Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan [email protected] [email protected].\nDepartment of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.",
"Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.",
"Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.",
"Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.\nResearch Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.",
"Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.",
"Division of Allergy and Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.",
"Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.",
"Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan [email protected] [email protected].\nResearch Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan."
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] | [] | 10.755836 | 5.666412 |
39150566 | 597 | Advances in manufacturing chimeric antigen receptor immune cell therapies. | Biomedical research has witnessed significant strides in manufacturing chimeric antigen receptor T cell (CAR-T) therapies, marking a transformative era in cellular immunotherapy. Nevertheless, existing manufacturing methods for autologous cell therapies still pose several challenges related to cost, immune cell source, safety risks, and scalability. These challenges have motivated recent efforts to optimize process development and manufacturing for cell therapies using automated closed-system bioreactors and models created using artificial intelligence. Simultaneously, non-viral gene transfer methods like mRNA, CRISPR genome editing, and transposons are being applied to engineer T cells and other immune cells like macrophages and natural killer cells. Alternative sources of primary immune cells and stem cells are being developed to generate universal, allogeneic therapies, signaling a shift away from the current autologous paradigm. These multifaceted innovations in manufacturing underscore a collective effort to propel this therapeutic approach toward broader clinical adoption and improved patient outcomes in the evolving landscape of cancer treatment. Here, we review current CAR immune cell manufacturing strategies and highlight recent advancements in cell therapy scale-up, automation, process development, and engineering. | [
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10.1016/j.jbi.2023.104367 | [
"Ramamurthy",
"Tommasi",
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"Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.\nDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.",
"Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.\nDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.",
"Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA. [email protected].\nDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA. [email protected]."
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39150543 | 598 | YAP1 Status Defines Two Intrinsic Subtypes of LCNEC with Distinct Molecular Features and Therapeutic Vulnerabilities. | Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine malignancy that, like small cell lung cancer (SCLC), is associated with the absence of druggable oncogenic drivers and dismal prognosis. In contrast to SCLC, however, there is little evidence to guide optimal treatment strategies, which are often adapted from SCLC and non-small cell lung cancer approaches.
To better define the biology of LCNEC, we analyzed cell line and patient genomic data and performed IHC and single-cell RNA sequencing of core needle biopsies from patients with LCNEC and preclinical models.
In this study, we demonstrate that the presence or absence of YAP1 distinguishes two subsets of LCNEC. The YAP1-high subset is mesenchymal and inflamed and is characterized, alongside TP53 mutations, by co-occurring alterations in CDKN2A/B and SMARCA4. Therapeutically, the YAP1-high subset demonstrates vulnerability to MEK- and AXL-targeting strategies, including a novel preclinical AXL chimeric antigen receptor-expressing T cell. Meanwhile, the YAP1-low subset is epithelial and immune-cold and more commonly features TP53 and RB1 co-mutations, similar to those observed in pure SCLC. Notably, the YAP1-low subset is also characterized by the expression of SCLC subtype-defining transcription factors, especially ASCL1 and NEUROD1, and as expected, given its transcriptional similarities to SCLC, exhibits putative vulnerabilities reminiscent of SCLC, including delta-like ligand 3 and CD56 targeting, as is with novel preclinical delta-like ligand 3 and CD56 chimeric antigen receptor-expressing T cells, and DNA damage repair inhibition.
YAP1 defines distinct subsets of LCNEC with unique biology. These findings highlight the potential for YAP1 to guide personalized treatment strategies for LCNEC. | [
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] | 2024-08-16 | 34 | 39150543 | [
"small cell lung cancer",
"cell line",
"Large cell neuroendocrine carcinoma",
"distinct subsets",
"pure SCLC",
"YAP1",
"optimal treatment strategies",
"personalized treatment strategies",
"SCLC and non-small cell lung cancer approaches",
"co-occurring alterations",
"TP53 mutations",
"SCLC",
"CD56 chimeric antigen receptor-expressing T cells",
"LCNEC",
"druggable oncogenic drivers",
"a novel preclinical AXL chimeric antigen receptor-expressing T cell",
"core needle biopsies",
"DNA damage repair inhibition",
"putative vulnerabilities",
"SCLC subtype-defining transcription factors",
"novel preclinical delta-like ligand",
"mutations",
"absence",
"genomic data",
"single-cell RNA",
"TP53",
"RB1 co",
"little evidence",
"vulnerability",
"unique biology"
] | [] | 0 | 10.1158/1078-0432.CCR-24-0361
10.12659/AJCR.908953
10.1038/s41379-021-00943-2
10.1093/annonc/mdt009
10.1186/s12885-023-10797-3
10.1016/j.lungcan.2019.11.004
10.1016/j.ccell.2020.12.014
10.1016/j.lungcan.2023.107418
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10.1016/j.ccell.2024.01.010 | [
"Stewart",
"Diao",
"Xi",
"Wang",
"Ramkumar",
"Serrano",
"Tanimoto",
"Rodriguez",
"Morris",
"Shen",
"Zhang",
"Yang",
"Hamad",
"Cardnell",
"Duarte",
"Sahu",
"Novegil",
"Weissman",
"Frumovitz",
"Kalhor",
"Solis Soto",
"da Rocha",
"Vokes",
"Gibbons",
"Wang",
"Heymach",
"Glisson",
"Byers",
"Gay"
] | [
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Surgery, Cooper Medical School of Rowan University, Camden, New Jersey.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina.",
"Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
"Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas."
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39149468 | 599 | Anti-CD7 allogeneic WU-CART-007 in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma: a phase 1/2 trial. | Relapsed/refractory T-cell acute lymphoblastic leukemia (ALL)/lymphoma (LBL) represent a significant unmet medical need. WU-CART-007 is a CD7-targeting, allogeneic, fratricide-resistant chimeric antigen receptor T cell product generated from healthy donor T cells. WU-CART-007 was evaluated in a phase 1/2 study with a 3 + 3 dose-escalation design followed by cohort expansion in relapsed/refractory T-ALL/LBL. Patients received one infusion of WU-CART-007 after standard or enhanced lymphodepleting chemotherapy. The primary objectives, to characterize safety and assess the composite complete remission rate, were met. Of 26 patients enrolled, 13 received the recommended phase 2 dose (RP2D) of 900 million cells of WU-CART-007 with enhanced lymphodepletion. The most common treatment-related adverse event was cytokine release syndrome (88.5%; 19.2% grade 3-4). Biochemical abnormalities consistent with grade 2 hemophagocytic lymphohistiocytosis were seen in one patient (3.8%). Grade 1 immune effector cell-associated neurotoxicity syndrome events (7.7%) and one grade 2 acute graft-vs-host disease event occurred. Grade 5 events (11.5%) were due to fungal infection and multi-organ failure. The composite complete remission rate was 81.8% among 11/13 patients evaluable for response at the RP2D. WU-CART-007 at the RP2D demonstrated a high response rate in patients with relapsed/refractory T-ALL/LBL and has the potential to provide a new treatment option. ClinicalTrials.gov registration: NCT04984356. | [
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] | 2024-08-16 | 24 | 39149468 | [
"healthy donor T cells",
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"registration",
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"relapsed/refractory T-ALL/LBL",
"the RP2D. WU-CART-007",
"ALL)/lymphoma",
"host",
"allogeneic"
] | [] | 0 | 10.21203/rs.3.rs-4676375/v1 | [
"Ghobadi",
"Aldoss",
"Maude",
"Bhojwani",
"Wayne",
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] | [
"Washington University School of Medicine.",
"City of Hope National Medical Center.",
"University of Pennsylvania.",
"CHLA.",
"Children's Hospital Los Angeles.",
"Peter MacCallum Cancer Center.",
"Vanderbilt University Medical Center.",
"Moffitt Cancer Center.",
"University of Wisconsin Carbone Cancer Center.",
"Erasmus Medical Center.",
"Erasmus Medical Center-Sophia Children's Hospital.",
"Prinses Máxima Centrum.",
"University Hospital Robert Debré and University Paris Diderot.",
"aphp hôpital saint louis paris.",
"Washington University in St Louis.",
"University of Southern California.",
"Mersana Therapeutics.",
"Washington University School of Medicine.",
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"Wugen.",
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"Wugen.",
"Wugen.",
"Wugen.",
"Wugen.",
"Wugen.",
"Wugen.",
"Alviso Clinical Research.",
"Wugen.",
"Washington University in St. Louis."
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] | [] | 6.434408 | 5.783544 |
Subsets and Splits