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

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P. M. Gershovich^1,2,a*, A. V. Karabelskii^1,2, A. B. Ulitin¹, and R. A. Ivanov¹

¹CJSC Biocad, 198515 St. Petersburg, Russia

²St. Petersburg State Chemical Pharmaceutical Academy, 197376 St. Petersburg, Russia

^* To whom correspondence should be addressed.

Received March 1, 2019; Revised April 4, 2019; Accepted April 4, 2019

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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.

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

DOI: 10.1134/S0006297919070022

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