title: Immunogenicity and efficacy of the novel cancer vaccine based on simian adenovirus and MVA vectors alone and in combination with PD-1 mAb in a mouse model of prostate cancer.
abstract: Prostate cancer possesses several characteristics that make it a suitable candidate for immunotherapy; however, prostate cancer vaccines to date demonstrate modest efficacy and low immunogenicity. The goal of the present pre-clinical study was to explore the immunogenic properties and protective efficacy of a novel prostate cancer immunotherapy based on the heterologous prime-boost viral-vectored vaccination platform. The simian adenovirus, ChAdOx1, and modified vaccinia Ankara virus, MVA, encoding a prostate cancer-associated antigen, the six transmembrane epithelial antigen of the prostate 1 (STEAP1), induced strong sustained antigen-specific CD8+ T-cell responses in C57BL/6 and BALB/c male mice. Unexpectedly, the high vaccine immunogenicity translated into relatively low protective efficacy in the murine transplantable and spontaneous models of prostate cancer. A combination of the vaccine with PD-1 blocking antibody significantly improved survival of the animals, with 80 % of mice remaining tumour-free. These results indicate that the ChAdOx1-MVA vaccination regime targeting STEAP1 combined with PD-1 therapy might have high therapeutic potential in the clinic.
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
authors.forename: Federica
authors.initials: F
authors.lastname: Cappuccini
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.|Department of Surgery and Oncology, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Stribbling
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: Pollock
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. irina.redchenko@ndm.ox.ac.uk.
authors.forename: Irina
authors.initials: I
authors.lastname: Redchenko
mesh_terms: D056704:Adaptive Immunity; D000261:Adenoviruses, Simian / Q000235:genetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007114:Immunization; D007117:Immunization, Secondary; D056747:Immunomodulation; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D061026:Programmed Cell Death 1 Receptor; C486624:Steap protein, mouse; D007371:Interferon-gamma
keywords: Immunogenicity; Prostate cancer; STEAP1; TRAMP model; Vaccine