Pharmacology of Chimeric Antigen Receptor-Modified T Cells

Annu Rev Pharmacol Toxicol. 2021 Jan 6:61:805-829. doi: 10.1146/annurev-pharmtox-031720-102211. Epub 2020 Oct 9.

Abstract

Cell-based immunotherapies using T cells that are engineered to express a chimeric antigen receptor (CAR-T cells) are an effective treatment option for several B cell malignancies. Compared with most drugs, CAR-T cell products are highly complex, as each cell product is composed of a heterogeneous mixture of millions of cells. The biodistribution and kinetics of CAR-T cells, following administration, are unique given the ability of T cells to actively migrate as well as replicate within the patient. CAR-T cell therapies also have multiple mechanisms of action that contribute to both their antitumor activity and their toxicity. This review provides an overview of the unique pharmacology of CAR-T cells, with a focus on CD19-targeting and B cell maturation antigen (BCMA)-targeting CAR-T cells.

Keywords: CAR; T cell; cancer; immunotherapy; pharmacology.

Publication types

  • Review

MeSH terms

  • B-Cell Maturation Antigen
  • Humans
  • Multiple Myeloma*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen* / metabolism
  • T-Lymphocytes / metabolism
  • Tissue Distribution

Substances

  • B-Cell Maturation Antigen
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen