Modular Chimeric Antigen Receptor Systems for Universal CAR T Cell Retargeting

Int J Mol Sci. 2020 Sep 30;21(19):7222. doi: 10.3390/ijms21197222.

Abstract

The engineering of T cells through expression of chimeric antigen receptors (CARs) against tumor-associated antigens (TAAs) has shown significant potential for use as an anti-cancer therapeutic. The development of strategies for flexible and modular CAR T systems is accelerating, allowing for multiple antigen targeting, precise programming, and adaptable solutions in the field of cellular immunotherapy. Moving beyond the fixed antigen specificity of traditional CAR T systems, the modular CAR T technology splits the T cell signaling domains and the targeting elements through use of a switch molecule. The activity of CAR T cells depends on the presence of the switch, offering dose-titratable response and precise control over CAR T cells. In this review, we summarize developments in universal or modular CAR T strategies that expand on current CAR T systems and open the door for more customizable T cell activity.

Keywords: CAR adaptor; adoptive immunotherapy; antibody; chimeric antigen receptor (CAR T); modular CAR T; split CAR; universal CAR T; universal immune receptor.

Publication types

  • Review

MeSH terms

  • Antigens, Neoplasm / drug effects
  • Antigens, Neoplasm / immunology
  • Cell Engineering / trends
  • Humans
  • Immunotherapy*
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / therapeutic use*
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / therapeutic use*
  • T-Lymphocytes / immunology

Substances

  • Antigens, Neoplasm
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen