Engineering Next-Generation CAR-T Cells for Better Toxicity Management

Int J Mol Sci. 2020 Nov 16;21(22):8620. doi: 10.3390/ijms21228620.

Abstract

Immunoadoptive therapy with genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) has revolutionized the treatment of patients with hematologic cancers. Although clinical outcomes in B-cell malignancies are impressive, researchers are seeking to enhance the activity, persistence, and also safety of CAR-T cell therapy-notably with a view to mitigating potentially serious or even life-threatening adverse events like on-target/off-tumor toxicity and (in particular) cytokine release syndrome. A variety of safety strategies have been developed by replacing or adding various components (such as OFF- and ON-switch CARs) or by combining multi-antigen-targeting OR-, AND- and NOT-gate CAR-T cells. This research has laid the foundations for a whole new generation of therapeutic CAR-T cells. Here, we review the most promising CAR-T cell safety strategies and the corresponding preclinical and clinical studies.

Keywords: CAR-T cell; cancer; chimeric antigen receptor; cytokine release syndrome; engineering; immunotherapy; toxicity.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytokine Release Syndrome / etiology
  • Cytokine Release Syndrome / metabolism
  • Cytokine Release Syndrome / prevention & control*
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Receptors, Chimeric Antigen*

Substances

  • Receptors, Chimeric Antigen