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Biochemistry (Moscow)

, Volume 84, Issue 7, pp 695–710 | Cite as

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

  • P. M. GershovichEmail author
  • A. V. Karabelskii
  • A. B. Ulitin
  • R. A. Ivanov
Review

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 anti-tumor 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.

Keywords

adoptive T cell immunotherapy of cancer chimeric antigen receptor CAR-T immuno-oncology immune checkpoint inhibitors cytokines interleukins 

Abbreviations

CAR

chimeric antigen receptor

CAR-T

T cell expressing a chimeric antigen receptor

IFN-γ

interferon-γ

IL

interleukin

MDSC

myeloid-derived suppressor cell

TAM

tumor-associated macrophage

TGF-β

transforming growth factor beta

Treg

regulatory T cell

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Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • P. M. Gershovich
    • 1
    • 2
    Email author
  • A. V. Karabelskii
    • 1
    • 2
  • A. B. Ulitin
    • 1
  • R. A. Ivanov
    • 1
  1. 1.CJSC BiocadSt. PetersburgRussia
  2. 2.St. Petersburg State Chemical Pharmaceutical AcademySt. PetersburgRussia

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