Abstract SY26-01: Vaccine induced immunity against cancer genes to prevent and treat pancreatic cancer

Abstract

Abstract Pancreatic cancer remains a “death sentence,” with the poorest survival rates reported for solid tumors. Escalating this problem is the fact that pancreatic cancer is among the most resistant cancers to traditional forms of therapy. But in this new era of targeted therapies, there is reason to hope that significant progress will be made in the development of new interventions for both treatment and prevention in the near future. In fact, we have entered into a new era of cancer therapies and are witnessing the rapid approval of antibodies and small molecule agents that inhibit cancer associated pathways. In the past few years we have also witnessed the approval of vaccines for cancer prevention (HPV vaccines, Gardasil, Cervarix) and cancer treatment (prostate cancer vaccine, Sipuleucel-T, Provenge); and the first immune modulating agent (Yervoy, Ipilimumab) that blocks the down regulatory signal, CTLA-4 on T cells, thereby enhancing immune activity against malignant melanoma. These groundbreaking examples have opened the floodgates for a whole new class of anticancer agents that harness the power of the immune system. Until recently, barriers to immunotherapy clinical successes for pancreatic cancer have been due to a lack of understanding of the immune pathways within the pancreatic tumor microenvironment that hinder successful immune responses even at the earliest stages of cancer development. Recent advances in our understanding of its immunobiology has identified new targets for developing cancer specific vaccines and new targets for modulating the tumor microenvironment to allow more potent activation and improved access of vaccine induced immune responses. We are just learning that non-neoplastic cells, including cancer-associated myofibroblasts, regulatory T cells, dendritic cells, myeloid-derived suppressor cells, and tumor-associated macrophages, are hijacked by pre-invasive and invasive cancer cells to create a tolerogenic tumor microenvironment. Current research is focused on elucidating the mechanisms of this cancer supporting polarization within the tumor microenvironment with the goal of tipping the balance in favor of an anticancer immunity. With the recent advances in molecular technologies and the development of relevant pancreatic cancer mouse models, it is now within our reach to dissect the inhibitory pathways within the pancreatic tumor microenvironment. This will in turn, lead to new therapeutic opportunities that will eliminate these barriers and convert this deadly cancer into a treatable and hopefully preventable disease. This presentation will provide new data supporting a role for targeting tumor initiating and metastasis supporting genes as immunotherapy for preventing tumor initiation and progression.