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

Cancer Immunol Immunother. 2016 Jun;65(6):701-13. doi: 10.1007/s00262-016-1831-8. Epub 2016 Apr 6.

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.

Keywords: Immunogenicity; Prostate cancer; STEAP1; TRAMP model; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adenoviruses, Simian / genetics*
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents / pharmacology
  • Cancer Vaccines / genetics*
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Disease Models, Animal
  • Genetic Vectors / genetics*
  • Humans
  • Immunization
  • Immunization, Secondary
  • Immunomodulation
  • Immunotherapy
  • Interferon-gamma / metabolism
  • Male
  • Mice
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Tumor Burden

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Cancer Vaccines
  • Programmed Cell Death 1 Receptor
  • Steap protein, mouse
  • Interferon-gamma