Remission-Stage Ovarian Cancer Cell Vaccine with Cowpea Mosaic Virus Adjuvant Prevents Tumor Growth

SIMPLE SUMMARY: Ovarian cancer survival rates are poor, with most deaths occurring from cancer recurrence following initial remission. Accordingly, there is a significant need for treatments that prevent relapse. Here, using a therapeutic vaccine against a mouse model of ovarian cancer, we evaluate a personalized vaccine that could be delivered to patients during their remission period. We show that mice that receive a combination of cowpea mosaic virus nanoparticles (CPMV) and irradiated tumor cells overwhelmingly reject tumor challenges in a T cell-dependent manner. Accordingly, we extend the demonstrated potential of CPMV as a vaccine adjuvant. We provide initial evidence that vaccines delivered during periods of clinical remission, using previously resected tumor tissue and an immune adjuvant, may comprise a feasible strategy of ovarian cancer treatment. ABSTRACT: Ovarian cancer is the deadliest gynecological malignancy. Though most patients enter remission following initial interventions, relapse is common and often fatal. Accordingly, there is a substantial need for ovarian cancer therapies that prevent relapse. Following remission generated by surgical debulking and chemotherapy, but prior to relapse, resected and inactivated tumor tissue could be used as a personalized vaccine antigen source. The patient’s own tumor contains relevant antigens and, when combined with the appropriate adjuvant, could generate systemic antitumor immunity to prevent relapse. Here, we model this process in mice to investigate the optimal tumor preparation and vaccine adjuvant. Cowpea mosaic virus (CPMV) has shown remarkable efficacy as an immunostimulatory cancer therapy in ovarian cancer mouse models, so we use CPMV as an adjuvant in a prophylactic vaccine against a murine ovarian cancer model. Compared to its codelivery with tumor antigens prepared in three other ways, we show that CPMV co-delivered with irradiated ovarian cancer cells constitutes an effective prophylactic vaccine against a syngeneic model of ovarian cancer in C57BL/6J mice. Following two vaccinations, 72% of vaccinated mice reject tumor challenges, and all those mice survived subsequent rechallenges, demonstrating immunologic memory formation. This study supports remission-stage vaccines using irradiated patient tumor tissue as a promising option for treating ovarian cancer, and validates CPMV as an antitumor vaccine adjuvant for that purpose.