Prostate cancer is a candidate for
immunotherapy because
cancer cells express tissue-specific
proteins that can be therapeutic targets. However,
immune checkpoint inhibitors and active immunization have performed poorly in clinical trials. We developed a novel virus-like particle (VLP)
vaccine composed of
bovine papillomavirus L1 protein engineered to display surface docking sites. We decorated VLPs with
peptides encoding
T cell epitopes from two
prostate cancer-associated
tumor antigens, prostate stem cell
antigen (PSCA), and
prostatic acid phosphatase (PAP-1 and PAP-2), and a neo-
antigen, stimulator of prostatic
adenocarcinoma-specific T cells (SPAS-1). The VLP
vaccines induced a mean frequency of
antigen-specific IFN-γ secreting CD8 + T cells of 2.9% to PSCA, 9.5% to SPAS-1, 0.03% to PAP-1, and 0.03% to PAP-2 in
tumor-bearing TRAMP mice. We treated TRAMP mice at 19-20 weeks of age, when mice have advanced stages of
carcinogenesis, with either VLP
vaccine, anti-PD1 antibody, or combination
immunotherapy. The VLP
vaccine alone or in combination with anti-PD1 antibody significantly reduced
tumor burden, while anti-PD1 antibody had a modest non-significant
therapeutic effect. All treatments significantly increased CD3 + and CD8 + T cell infiltration into
tumor tissue compared to control mice, and combination
therapy resulted in significantly greater CD3 + and CD8 + T cell infiltration than monotherapy. Reduction in
tumor burden in
vaccine-treated mice was inversely correlated with CD8 + T cell numbers in
tumor tissue. No other
immunotherapy has shown efficacy in this animal model of advanced
prostate cancer, making bovine papillomavirus VLPs an attractive
vaccine technology to test in patients with metastatic
prostate cancer.