Antigen-specific oncolytic MV-based tumor vaccines through presentation of selected tumor-associated antigens on infected cells or virus-like particles

Sci Rep. 2017 Dec 4;7(1):16892. doi: 10.1038/s41598-017-16928-8.

Abstract

Recombinant vaccine strain-derived measles virus (MV) is clinically tested both as vaccine platform to protect against other pathogens and as oncolytic virus for tumor treatment. To investigate the potential synergism in anti-tumoral efficacy of oncolytic and vaccine properties, we chose Ovalbumin and an ideal tumor antigen, claudin-6, for pre-clinical proof of concept. To enhance immunogenicity, both antigens were presented by retroviral virus-like particle produced in situ during MV-infection. All recombinant MV revealed normal growths, genetic stability, and proper expression and presentation of both antigens. Potent antigen-specific humoral and cellular immunity were found in immunized MV-susceptible IFNAR-/--CD46Ge mice. These immune responses significantly inhibited metastasis formation or increased therapeutic efficacy compared to control MV in respective novel in vivo tumor models using syngeneic B16-hCD46/mCLDN6 murine melanoma cells. These data indicate the potential of MV to trigger selected tumor antigen-specific immune responses on top of direct tumor lysis for enhanced efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Autoantibodies / blood
  • Autoantibodies / metabolism
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Claudins / genetics
  • Claudins / immunology
  • Claudins / metabolism
  • Immunity, Cellular
  • Immunity, Humoral
  • Interferon-gamma / metabolism
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Measles virus / genetics*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Transgenic
  • Oncolytic Virotherapy
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology*
  • Vaccines, Virus-Like Particle / therapeutic use
  • Vero Cells

Substances

  • Antigens, Neoplasm
  • Autoantibodies
  • Cancer Vaccines
  • Claudins
  • Vaccines, Virus-Like Particle
  • Interferon-gamma
  • Ovalbumin
  • claudin 6