STING-Activating GM-CSF Secreting Allogeneic Pancreas Tumor Cell Vaccine Therapy

DESCRIPTION (provided by applicant): The incidence of pancreatic adenocarcinoma (PDA) is gt 45,000 cases per year in the US and is increasing. While new chemotherapy regimens such as Abraxane and FOLFIRINOX extend overall survival, none offer the promise of long-term disease-free survival. We submit that immunotherapy can be an effective and durable therapeutic option for PDA. Here we extend both our published and unpublished clinical results and propose to develop a more advanced immunotherapy regimen forPDA by enhancing the immunologic potency of irradiated GM-CSF producing allogeneic tumor cells, known as GVAX. We hypothesize that a critical missing component of GVAX vaccines has been a potent DC activator. STINGVAX is based on a novel and highly active small molecule immune stimulator - cyclic-dinucleotides (CDNs) - which activate innate immunity through targeting the cytoplasmic, TLR-independent pathogen recognition receptor STING (Stimulator of Interferon Genes). CDNs are co-formulated with G