期刊
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
卷 45, 期 4, 页码 425-435出版社
WILEY
DOI: 10.1111/ijlh.14121
关键词
CAR T-cell; imaging flow cytometry; immunotherapy; leukaemia; lymphoma
类别
Chimeric antigen receptor (CAR) T-cell therapy is a customized immunotherapy for hematological malignancies, using genetically engineered T-cells to recognize and kill tumor cells. CAR T-cells harness the cytotoxic capacity of a patient's immune system and have the potential to generate robust anti-tumor responses.
Chimeric 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.
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