Manipulating the Metabolism to Improve the Efficacy of CAR T-Cell Immunotherapy

Cells. 2020 Dec 24;10(1):14. doi: 10.3390/cells10010014.

Abstract

The adoptive transfer of the chimeric antigen receptor (CAR) expressing T-cells has produced unprecedented successful results in the treatment of B-cell malignancies. However, the use of this technology in other malignancies remains less effective. In the setting of solid neoplasms, CAR T-cell metabolic fitness needs to be optimal to reach the tumor and execute their cytolytic function in an environment often hostile. It is now well established that both tumor and T cell metabolisms play critical roles in controlling the immune response by conditioning the tumor microenvironment and the fate and activity of the T cells. In this review, after a brief description of the tumoral and T cell metabolic reprogramming, we summarize the latest advances and new strategies that have been developed to improve the metabolic fitness and efficacy of CAR T-cell products.

Keywords: Chimeric Antigen Receptor T cells; cancer; combined therapy; immunotherapy; metabolic reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Neoplasm / immunology
  • Humans
  • Immunotherapy, Adoptive*
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Receptors, Chimeric Antigen / immunology*
  • T-Lymphocytes* / cytology
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism
  • Tumor Microenvironment / immunology*

Substances

  • Antigens, Neoplasm
  • Receptors, Chimeric Antigen