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CAR-T CELL THERAPY CAUSES INFLAMMATION BY IL-1 WHICH ACTIVATES INFLAMMATORY CYTOKINE MAST CELLS: ANTI-INFLAMMATORY ROLE OF IL-37
Vol 33, Issue 6, 2019
Abstract
Chimeric antigen receptor (CAR) T cells are genetically modified T cells that act against cancer. When CAR-T cells are administered they can trigger inflammatory cytokines and increase toxicity. Interleukin (IL)-1 is the classic cytokine that mediates inflammatory reactions including those that occur in CAR-T-cell therapy. IL-1 also induces IL-33 in mast cells (MCs), amplifying the allergic reaction. IL- 37 (ILF7) is an IL-1 family member which binds IL-18 receptor alpha (IL-18Rα) chain and suppresses innate and acquired immunity. IL-37 is an anti-inflammatory cytokine which inhibits pro-inflammatory cytokines including IL-1 and IL-33. Here, we hypothesize that inflammation and toxicity generated in tumor CAR-T therapy could be inhibited by IL-37, contributing to an improvement in the treatment of tumors with CAR-T therapy.
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Copyright (c) 2019 Al. Caraffa, C.E. Gallenga, S.K. Kritas, G. Ronconi, P.Di Emidio, P. Conti
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Medical Genetics, University of Torino Medical School, Italy
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy