Stinginn, LLC

Human Specific Sting Agonists for the Treatment of Cancer - Project Summary Cellular Innate Immune Sensors, Such as Sting (stimulator of Interferon Genes), Have Evolved to Detect Microbial Infection of the Cell (1-3). Sting Controls the Potent Cytosolic Dna-stimulated Innate Immune Pathways and Is Activated by Cyclic Dinucleotides (CDNS) Such as Cyclic Di-gmp and Cyclic-di-amp Secreted by Intracellular Bacteria Following Infection. Alternatively, Sting Can Be Activated by Cyclic Gmp-amp (CGAMP) Generated by a Cellular Cgamp Synthase Cgas (MB21D1) After Association With Aberrant Cytosolic Dsdna Species, Which Can Include Microbial Dna or Self-dna Leaked From the Nucleus (4). Association With CDNS Enables Sting to Activate the Production of Type I Interferon (IFN) and Pro-inflammatory Cytokines, Which Facilitate Adaptive Immunity (3). Aside From Being Critical for the Protection Against Microbial Infection, Sting Signaling Has Been Shown to Be Essential for Facilitating Robust Anti-tumor Immunity. Regulation of the Immune System to Stimulate Anti-tumor Cytotoxic T Cell Responses Is Proving to Be a Powerful Approach for the Effective Treatment of a Variety of Cancers. for Example, Sting Agonists, Based on Synthetic CDNS, Have Been Shown to Exert Potent Anti-tumor Properties Likely by Stimulating Apcs and Are Now Being Evaluated in Phase I Trials for the Treatment of Cancer. However, Such CDNS Are Highly Labile and Do Not Exert Potent Activity When Given Systemically. This Has Limited Their Use/evaluation to Intratumoral and Oral Administration. Here, We Describe a New Generation of Novel Small Sting Agonists That Activate Sting Signaling, That Appear Superior to Existing CDN’S, for Evaluation in Anti-tumor Therapeutic Strategies. the Compounds Have Been Generated by Stinginn LLC, Based in Miami, in Collaboration With the University of Miami School of Medicine, FL.