Abstract
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.