Revving the CAR - Combination strategies to enhance CAR T cell effectiveness

Blood Rev. 2021 Jan:45:100695. doi: 10.1016/j.blre.2020.100695. Epub 2020 May 5.

Abstract

Chimeric antigen receptor (CAR) T cell therapy is currently approved for treatment of refractory B-cell malignancies. Response rates in these diseases are impressive by historical standards, but most patients do not have a durable response and there remains room for improvement. To date, CAR T cell activity has been even more limited in solid malignancies. These limitations are thought to be due to several pathways of resistance to CAR T cells, including cell-intrinsic mechanisms and the immunosuppressive tumor microenvironment. In this review, we discuss current experimental strategies that combine small molecules and monoclonal antibodies with CAR T cells to overcome these resistance mechanisms. We describe the biological rationale, pre-clinical data and clinical trials in progress that test the efficacy and safety of these combinations.

Keywords: CAR T cell therapy; Combination therapy; Resistance to CAR T cells.

Publication types

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

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Drug Evaluation, Preclinical
  • Humans
  • Immunomodulation
  • Immunotherapy, Adoptive* / methods
  • Neoplasms / etiology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Chimeric Antigen / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Treatment Outcome
  • Tumor Microenvironment / immunology

Substances

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