Simons et al. designed a virus-like particle vaccine comprising bovine papillomavirus L1 proteins with docking sites loaded with prostate cancer-associated (PSCA, PAP-1, PAP-2) and neoantigen (SPAS-1) peptides. In TRAMP mice with advanced prostate cancer, the vaccine induced antigen-specific responses, and significantly reduced total prostate weight, both alone and in combination with anti-PD-1; anti-PD-1 alone was ineffective. All treatments increased CD3+ and CD8+ T cell infiltration into tumors, with combination therapy being most effective. Prostate weight negatively correlated with CD8+ T cell numbers in tumors of mice treated with vaccine alone.
Contributed by Anna Scherer
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-gamma 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.
Author Info: (1) Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA. Center for Comparative Medicine, Baylor College of M
Author Info: (1) Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA. Center for Comparative Medicine, Baylor College of Medicine, Houston, TX, USA. (2) The Department of Pediatrics, Johns Hopkins University, 600 North Wolfe Street, Blalock Building 1153, Baltimore, MD, 21287, USA. Laboratory of Virology, Department of Molecular Medicine, and Institute Pasteur-Cenci Bolognetti Foundation, Sapienza University, Rome, Italy. (3) The Department of Pediatrics, Johns Hopkins University, 600 North Wolfe Street, Blalock Building 1153, Baltimore, MD, 21287, USA. (4) The Department of Pediatrics, Johns Hopkins University, 600 North Wolfe Street, Blalock Building 1153, Baltimore, MD, 21287, USA. rviscid1@jhmi.edu.
