Abstract 5567: In vivo administration of the STING agonist, JNJ-67544412, leads to complete regression of established murine subcutaneous tumors

STING (Stimulator of Interferon Genes) is an important mediator of innate and adaptive immunity that responds to invading cytosolic bacterial and viral pathogens, and double stranded DNA from transformed cells. Activation of the cGAS-STING pathway leads to pleiotropic cytokine (IFN-α, IFN-β, TNF-α, IL-6) production, maturation and activation of macrophages, and MHC class II expressing dendritic cells (DCs) with generation of CD8+ T cells. JNJ-67544412 (JNJ-4412) is a cyclic dinucleotide (CDN) developed as a STING agonist. JNJ-4412 binds both mouse and human STING and is more potent binding all the major human STING alleles than most other STING CDN agonists. JNJ-4412 phosphorylate STING and IRF3 and induces high levels of IFNβ and other cytokines in M1 and M2 macrophages, dendritic cells, and monocytes. In syngeneic mouse tumor studies, JNJ-4412 was dosed intratumorally (i.t.) on a q3d x 3 or qweekly schedule resulting in significant tumor regression, complete cures and long-lasting antitumor immunity. Body weight loss (