Immunoprevention of pancreatic cancer

Background: Pancreatic cancer (PC) is considered an incurable disease due to late diagnosis, rapid spread and negligible response treatment methods, with a 5-year survival rate of only 7%. Hence, there is an urgency in developing novel strategies for PC prevention. This review is focused on discussing the challenges in understanding complex immune functions in tumor microenvironment and host-induced immune responses against tumors, selection of antigens for development of preventive vaccines, lessons from immunoprevention clinical trials and challenges in developing future vaccines. Methods: 65 original articles were referenced from various sources, based on immunoprevention or criteria pertaining to tumor antigens and immune responses in PC. All these articles were analyzed for the method details and results obtained, and the existing challenges were derived for successful development of clinical immunoprevention strategies. Results: The analysis of these articles and our experience with preclinical efficacy evaluations of various preventive approaches against PC helped in identifying specific tumor antigens as targets which can overcome tumor cell immune suppression. This review discussed the status of primary, secondary and tertiary preventive vaccines and reasons for failure of therapeutic vaccines. The key parameters for effective vaccination were identified, including stage of the disease for vaccination efficacy, use of appropriate animal models for development of preventive vaccines. Potential of chemopreventive agents as adjuvants in immunoprevention was discussed. This review identified new challenges for development of immunopreventive vaccines. Conclusion: This review analyzed various aspects of vaccine development for immunoprevention of PC and emphasized the challenges for development of immunoprevention strategies.