The Role of Checkpoint Inhibitors and Cytokines in Adoptive Cell-Based Cancer Immunotherapy with Genetically Modified T Cells

Biochemistry (Mosc). 2019 Jul;84(7):695-710. doi: 10.1134/S0006297919070022.

Abstract

This review focuses on the structure and molecular action mechanisms of chimeric antigen receptors (CARs) and major aspects of the manufacturing and clinical application of products for the CAR-T (CAR-modified T lymphocyte) therapy of hematological and solid tumors with special emphasis on the strategies for combined use of CAR-T therapy with immuno-oncological monoclonal antibodies (checkpoint inhibitors) and cytokines to boost survival, persistence, and antitumor efficacy of CAR-T therapy. The review also summarizes preclinical and clinical data on the additive effects of the combined use of CAR-T therapy with interleukins and monoclonal antibodies targeting immune checkpoints.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Neoplasm / immunology
  • Cytokines / therapeutic use*
  • Drug Therapy, Combination
  • Genetic Vectors
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunotherapy, Adoptive*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Receptors, Chimeric Antigen / chemistry
  • Receptors, Chimeric Antigen / metabolism*
  • Receptors, Immunologic
  • T-Lymphocytes / immunology*
  • Treatment Outcome
  • Tumor Microenvironment / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Cytokines
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Chimeric Antigen
  • Receptors, Immunologic