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

P. M. Gershovich1,2,a*, A. V. Karabelskii1,2, 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
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.
KEY WORDS: adoptive T cell immunotherapy of cancer, chimeric antigen receptor, CAR-T, immuno-oncology, immune checkpoint inhibitors, cytokines, interleukins

DOI: 10.1134/S0006297919070022