Chimeric antigen receptor T‐cells: Properties, production, and quality control

Abstract

AbstractChimeric antigen receptor (CAR) T‐cell therapy is a novel adoptive T‐cell immunotherapy for haematological malignancies. First introduced into clinical practice in 2017, CAR T‐cell therapy is now finding its place in the management of lymphoid malignancies, primarily of B‐cell lineage, including lymphoblastic leukaemia, non‐Hodgkin lymphoma and plasma cell myeloma, with remarkable therapeutic outcomes. CAR T‐cells are a customised therapeutic product for each patient. Manufacture commences with collection of autologous T‐cells, which are then genetically engineered ex vivo to express transmembrane CARs. These chimeric proteins consist of an antibody‐like extracellular antigen‐binding domain, to recognise specific antigens on the surface of tumour cells (e.g. CD19), linked to the intracellular co‐stimulatory signalling domains of a T‐cell receptor (e.g. CD137). The latter is required for in vivo CAR T‐cell proliferation, survival, and durable efficacy. Following reinfusion, CAR T‐cells harness the cytotoxic capacity of a patient's immune system. They overcome major mechanisms of tumour immuno‐evasion and have potential to generate robust cytotoxic anti‐tumour responses. This review discusses the background to CAR T‐cell therapies, including their molecular design, mechanisms of action, methods of production, clinical applications and established and emerging technologies for CAR T‐cell evaluation. It highlights the need for standardisation, quality control and monitoring of CAR T‐cell therapies, to ensure their safety and efficacy in clinical management.