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Introduction: Treatment options for metastatic prostate cancer are limited and cures are rare. In other cancers immunotherapy has shown remarkable efficacy in certain patient subsets particularly when combined with other treatment modalities. Our previous work showed that combining radiation and vaccine therapy slows the growth of syngeneic prostate cancer in mice more effectively than single modality treatment arms. Here we tested the hypothesis that addition of immune checkpoint inhibitors targeting the PD1/PD-L1 axis further improves efficacy of the dual radiation/vaccine treatment.

Methods: Mice were injected with tumor cells expressing human prostate specific antigen (TPSA-23). The mice were divided into six groups. One group received no therapy. One group received vaccine and radiation alone. The other four groups received radiation, vaccine, and either a PD-1 or PD-L1 inhibitory antibody or its corresponding isotype control. Tumors were measured twice weekly, growth curves generated, and results were analyzed using a 2-way ANOVA test.

Results: Mice receiving radiation and vaccine therapy demonstrated delayed tumor growth as compared to untreated mice. Addition of the anti-PD- 1 antibody was significantly (p=0.0005) more effective than dual treatment in delaying tumor growth when compared to corresponding isotype controls at early time points. However, overall survival was not significantly improved by either antibody targeting the PD1/PD-L1 axis beyond the growth inhibition achieved by the radiation/vaccine combination.

Conclusions: Our results suggest that PD1 checkpoint blockade may have utility when added to radiation/vaccine immunotherapy in a murine prostate cancer model. The molecular correlates of these effects are yet to be determined.