Antigen-Specific T Cell Recall Assay To Screen Drugs For Off-Target Effects

Published: Aug. 10, 2020, 12:01 p.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.10.241869v1?rss=1 Authors: Kleiman, E., Sierra, G., Magcase, D., George, M. V., Daftarian, P. M. Abstract: Extracellular adenosine suppresses T cell immunity in the tumor microenvironment. We have developed an in vitro recall assay utilizing a sequential adenosine dosing regimen guide for testing drug off-target effects on memory T cell expansion/function. As a proof of principle, we show low dose adenosine analog GS-5734 does not alter memory T cell recall whereas toxicity observed at high dose favors antigen-specific memory T cell survival/proliferation over non-specific CD8+ T cells. Parent drug GS-445124 at high dosage interferes with antigen-specific T cell recall without cellular toxicity. Despite similar chemical structure, these drugs displayed opposing effects on memory T cell expansion. This assay platform has broad utility in screening memory T cell off-target effects. Copy rights belong to original authors. Visit the link for more info