Abstract Our laboratory developed cell based cancer vaccines (STINGVAX) that was formulated with cyclic dinucleotides that and sensed by STING to phosphorylate interferon regulatory factor3 (IRF3) and nuclear factor kappa-light-chain-enhancer (NF-κB) to induce B cells and myeloid cells to secrete IFN-β. IFN-β can active NK cells through Tyk2-STAT1 signaling pathway, and we found increased number of activated NK cells in tumor bearing mice treated with STINGVAX. In the context of formulation with GM-CSF secreting cellular vaccines, the anti-tumor effect of CDN was dependent on IFNα/β receptors. We found that CDN activated NK cells both in vitro and in vivo, and at the molecular level, CDN increased TYK2-STAT1 signaling. When we tested STINGVAX's anti-tumor efficacy with NK depletion, its anti-tumor effect was abrogated.
Citation Format: Juan Fu, Qi Zhen, Drew Pardoll, Tom Dubensky, Young Kim. Cyclic dinucleotides (CDNs) activated DC and NK cells in antitumor immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B42.