CAR T-cells; Hematological malignancies; Long-term remissions; Preclinical studies; Predictors of response; Translational immunology; Hematology; Oncology
Abstract :
[en] Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in achieving durable and potentially curative responses in patients with hematological malignancies. CARs are tailored fusion proteins that direct T cells to a specific antigen on tumor cells thereby eliciting a targeted immune response. The approval of several CD19-targeted CAR T-cell therapies has resulted in a notable surge in clinical trials involving CAR T cell therapies for hematological malignancies. Despite advancements in understanding response mechanisms, resistance patterns, and adverse events associated with CAR T-cell therapy, the translation of these insights into robust clinical efficacy has shown modest outcomes in both clinical trials and real-world scenarios. Therefore, the assessment of CAR T-cell functionality through rigorous preclinical studies plays a pivotal role in refining therapeutic strategies for clinical applications. This review provides an overview of the various in vitro and animal models used to assess the functionality of CAR T-cells. We discuss the findings from preclinical research involving approved CAR T-cell products, along with the implications derived from recent preclinical studies aiming to optimize the functionality of CAR T-cells. The review underscores the importance of robust preclinical evaluations and the need for models that accurately replicate human disease to bridge the gap between preclinical success and clinical efficacy.
Disciplines :
Hematology Immunology & infectious disease
Author, co-author :
Arunachalam, Arun K; Cell Therapy & Immuno-Engineering Program, Center for Immunotherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, United States of America
GREGOIRE, Céline ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie clinique ; Cell Therapy & Immuno-Engineering Program, Center for Immunotherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, United States of America
Coutinho de Oliveira, Beatriz; Cell Therapy & Immuno-Engineering Program, Center for Immunotherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, United States of America
Melenhorst, Jan Joseph; Cell Therapy & Immuno-Engineering Program, Center for Immunotherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, United States of America. Electronic address: melenhj@ccf.org
Language :
English
Title :
Advancing CAR T-cell therapies: Preclinical insights and clinical translation for hematological malignancies.
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