Advances in modular control of CAR-T therapy with adapter-mediated CARs

Adv Drug Deliv Rev. 2022 Aug:187:114358. doi: 10.1016/j.addr.2022.114358. Epub 2022 May 23.

Abstract

Protein engineering has contributed to successes in the field of T cell-based immunotherapy, including chimeric antigen receptor (CAR) T cell therapy. CAR T cell therapy has become a pillar of cancer immunotherapy, demonstrating clinical effectiveness against B cell malignancies by targeting the B cell antigen CD19. Current gene editing techniques have limited safety controls over CAR T cell activity, which presents a hurdle for control of CAR T cells in patients. Alternatively, CAR T cell activity can be controlled by engineering CARs to bind soluble adapter molecules that direct the interaction between the CAR T cell and target cell. The flexibility in this adapter-mediated approach overcomes the rigid specificity of traditional CAR T cells to allow targeting of multiple cell types. Here we describe adapter CAR T technologies and how these methods emphasize the growing role of protein engineering in the design of programmable tools for T cell therapies.

Keywords: Adoptive cell therapy; Cancer immunotherapy; Chimeric antigen receptors; Protein engineering; Synthetic biology.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, CD19 / metabolism
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Chimeric Antigen*
  • T-Lymphocytes

Substances

  • Antigens, CD19
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen