Targeting the A3 adenosine receptor to treat cytokine release syndrome in cancer immunotherapy

Drug Design, Development and Therapy
Shira Cohen, Pnina Fishman

Abstract

Cancer patients undergoing immunotherapy may develop cytokine release syndrome (CRS), an inflammatory cytokine storm condition, followed by neurotoxic manifestations and may be life-threatening. The current treatments for CRS successfully reduce the inflammatory response but may limit the anticancer effect of the given immunotherapy and fail to overcome the neurotoxic adverse events. Adenosine, a ubiquitous purine nucleoside, induces a plethora of effects in the body via its binding to four adenosine receptors A1, A2a, A2b, and the A3. Highly selective agonists to the A3 adenosine receptor act as inhibitors of proinflammatory cytokines, possess robust anti-inflammatory and anticancer activity, and concomitantly, induce neuroprotective effects. Piclidenoson and namodenoson belong to this group of compounds, are effective upon oral administration, show an excellent safety profile in human clinical studies, and therefore, may be considered as drug candidates to treat CRS. In this article, the detailed anti-inflammatory characteristics of these compounds and the rationale to use them as drugs to combat CRS are described.

Associated Clinical Trials

Citations

Mar 19, 2020·Pain·Kenneth A JacobsonDaniela Salvemini
Apr 16, 2019·Frontiers in Cellular Neuroscience·Kenneth A JacobsonZhan-Guo Gao
Jun 14, 2019·Expert Opinion on Therapeutic Targets·Stefania MerighiStefania Gessi
Oct 20, 2019·International Journal of Molecular Sciences·Zhan-Guo Gao, Kenneth A Jacobson
Jan 15, 2021·World Journal of Surgical Oncology·Zhengyu FangWenxi Yan
May 4, 2021·Frontiers in Pharmacology·Livio LuongoDaniela Salvemini
Jul 11, 2021·Life Sciences·Shahin HallajFarhad Jadidi-Niaragh

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