A small molecule termed M04 behaves as a novel agonist of human STING. Importantly, we find that the molecule exhibits a differential ability to activate STING based on the allelic variant examined. Furthermore, while M04 is inactive in mice, expression of human STING in mouse cells rescues reactivity to the compound. Using primary human cells in ex vivo assays we were also able to show that M04 is capable of simulating innate responses important for adaptive immune activation such as cytokine secretion, dendritic cell maturation, and T cell cross-priming. Collectively, this work demonstrates the conceivable utility of a novel agonist of human STING both as a research tool for exploring STING biology and as an immune potentiating molecule. SOURCE: Victor DeFilippis (defilipp@ohsu.edu) - DeFilippis Oregon Health & Science University

Pluto Bioinformatics

GSE152179: Characterization of a Novel Compound that Stimulates STING-Mediated Innate Immune Activity in an Allele-Specific Manner