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

Authors Cohen S, Fishman P

Received 20 November 2018

Accepted for publication 8 January 2019

Published 30 January 2019 Volume 2019:13 Pages 491—497

DOI https://doi.org/10.2147/DDDT.S195294

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Manfred Ogris


Shira Cohen, Pnina Fishman

Can-Fite BioPharma Ltd., Kiryat-Matalon, Petah-Tikva 49170, Israel

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.

Keywords: A3, adenosine receptor, cytokine release syndrome, treatment, immunotherapy


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