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

Int J Lab Hematol. 2023 Aug;45(4):425-435. doi: 10.1111/ijlh.14121. Epub 2023 Jun 20.

Abstract

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.

Keywords: CAR T-cell; imaging flow cytometry; immunotherapy; leukaemia; lymphoma.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents*
  • Humans
  • Multiple Myeloma* / therapy
  • Quality Control
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Chimeric Antigen* / genetics
  • T-Lymphocytes

Substances

  • Receptors, Chimeric Antigen
  • Receptors, Antigen, T-Cell
  • Antineoplastic Agents