Onse. CD40L can also reduce the amount of myeloid suppressor cells and M2 macrophages too as induce apoptosis in CD40 constructive tumor cells. 4-1BB ligand (4-1BBL) interactions with its receptor 4-1BB on T cells results in activation and survival on the cells and may expand memory T cells. Herein, we PDE6 Inhibitor supplier present an oncolytic adenovirus with a CMV-driven transgene cassette containing the human transgenes for any trimerized, membrane-bound CD40 ligand (TMZ-CD40L) along with the full length 4-1BBL. Strategies Pancreatic cell lines and exocrine cells from healthier donors were infected with LOAd703 and analyzed for cell death 48 and 72 hours post-infection with MTS-assay. Immunodeficient mice with established human Panc01 tumors had been treated twice per week for three weeks and evaluated for tumor size. Each the in vitro and in vivo experiments had been repeated in mixture with gemcitabine. Dendritic cells have been infected with all the virus and evaluated by flow cytometry and ProSeek. The dendritic cells have been also pulsed with CMV peptides and co-cultured with autologous CD14- cells to investigate the expansion of CMV+ T cells by flow cytometry. Final results LOAd703 decreased the viability of pancreatic tumor cells at each 48 hours and 72 hours as when compared with cells infected with a nonreplication competent virus but spared healthier exocrine cells. Mice treated with LOAd703 had a decreased tumor burden compared to PBS treated animals. LOAd703 might be successfully combined with gemcitabine without having any adverse effects on oncolysis each in vitro and in vivo. Dendritic cells infected with LOAd703 showed a mature phenotype with expression of CD83, CD86, and secretion of cytokines, chemokines including IL12p70 and IFN. The dendritic cells were also functional and could expand antigen-specific CMV+ T cells and NK cells. Conclusions In conclusion, LOAd703 is actually a novel oncolytic virus that targets each the tumor with oncolysis as well as the immune system with Th1 kind response from dendritic cells and an expansion of antigen-specific T cells. The subsequent step is to bring the virus from the lab bench towards the bedside inside a clinical trial to elucidate its effect in pancreatic cancer (NCT02705196). P312 An oncolytic virus targeting tumor cell survival, desmoplasia and immune activation in pancreatic cancer Emma Eriksson1, Ioanna Milenova2, Rafael Moreno3, Ramon Alemany3, Angelica Loskog4 1 Uppsala University, Uppsala, Sweden; 2Uppsala University, SSTR3 Agonist manufacturer Amsterdam, Netherlands; 3Institut Catald’Oncologia, Barcelona, Spain; 4Uppsala University, Lokon Pharma AB, Uppsala, Sweden Correspondence: Emma Eriksson ([email protected]) Journal for ImmunoTherapy of Cancer 2016, four(Suppl 1):P312 Background The tumor microenvironment supports the tumor cells. In pancreatic cancer, stellate cells, immune cells and extracellular matrix compose the majority of your lesions and build a condition known as desmoplasia. IL6 drives STAT3 activation top to transforming development aspect (TGF) beta and collagen form 1 production. TGF beta also promotes immunosuppression by inhibition of T cells and expansion of T regulatory cells (Tregs). Therefore, IL6, which can be overexpressed in pancreatic cancer, is amongst the regulators of desmoplasia. Further, IL6 is linked to poor prognosis of pancreatic cancer. To be able to target each IL6 and induce immune activation, the oncolytic adenovirus LOAd713 was developed. It is double-armed with an anti-IL6 receptor antibody single chain fragment (aIL6R scFv) aiming to disrupt ILsignaling.