Adenosine-related small molecules show utility of recall antigen assay to screen compounds for off-target effects on memory T cells.

ABSTRACT: Extracellular adenosine suppresses T cell immunity in the tumor microenvironment and in vitro treatment of memory T cells with adenosine can suppress antigen-mediated memory T cell expansion. We describe utilizing the recall antigen assay platform to screen small molecule drug off-target effects on memory T cell expansion/function using a dosing regimen based on adenosine treatment. As a proof of principle, we show low dose GS-5734, a monophosphoramidate prodrug of an adenosine analog, does not alter memory T cell recall at lower doses whereas toxicity observed at high dose favors antigen-specific memory T cell survival/proliferation over non-specific CD8⁺ T cells. Conversely, parent nucleoside GS-441524 at high dosage does not result in cellular toxicity and reduces antigen-spe

SUBMITTER: Kleiman E 

PROVIDER: S-EPMC8100288 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature