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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

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 eff...

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Detalles Bibliográficos
Autores principales: Cappuccini, Federica, Stribbling, Stephen, Pollock, Emily, Hill, Adrian V. S., Redchenko, Irina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880633/
https://www.ncbi.nlm.nih.gov/pubmed/27052571
http://dx.doi.org/10.1007/s00262-016-1831-8
Descripción
Sumario: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.