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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
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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
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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
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Journal Article
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
2016
Overview
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.
Publisher
Springer Berlin Heidelberg,Springer Nature B.V
Subject
/ Adenoviruses, Simian - genetics
/ Animals
/ Antibodies, Monoclonal - pharmacology
/ Antigen Presentation - immunology
/ Antigens
/ Antigens, Neoplasm - immunology
/ Antineoplastic Agents - pharmacology
/ Cancer Vaccines - immunology
/ Cloning
/ Humans
/ Interferon-gamma - metabolism
/ Male
/ Medicine
/ Mice
/ Oncology
/ Original
/ Programmed Cell Death 1 Receptor - antagonists & inhibitors
/ Prostatic Neoplasms - genetics
/ Prostatic Neoplasms - immunology
/ Prostatic Neoplasms - pathology
/ Prostatic Neoplasms - therapy
/ T-Lymphocyte Subsets - immunology
