Pancreatic cancer is a devastating disease with poor overall survival. Pancreatic cancer is not only resistant to conventional chemotherapy but also to the novel toolbox of checkpoint blockade antibodies. … Resistance to checkpoint immunotherapy is likely due to the low presence of tumor-infiltrating T cells which in turn depends on a low mutational burden and high infiltration of immunosuppressive myeloid cells among other immune escape mechanisms. Our goal is to inflame the tumor microenvironment by immunostimulatory gene therapy to kick-start anti-tumor responses via increased antigen presentation and subsequent activation of both T and NK cells. We are utilizing and oncolytic adenovirus encoding a human designed trimerized, membrane-bound CD40L and full length 4-1BBL (LOAd703) for gene transfer. The mechanism of action and preclinical work leading to clinical lead selection will be discussed. Further, preliminary results from ongoing clinical trials will be presented including safety, response data and biopsy proteomics.