Protective immunity elicited by measles vaccine exerts anti-tumor effects on measles virus hemagglutinin gene-modified cancer cells in a mouse model

J Cancer Res Clin Oncol. 2018 Oct;144(10):1945-1957. doi: 10.1007/s00432-018-2720-7. Epub 2018 Aug 6.

Abstract

Purpose: Measles vaccine is widely used in China to prevent the measles virus (MV) infection. People immunized with measles vaccine can obtain long-term protective immunity. Measles virus surface glycoprotein hemagglutinin (H) can also induce MV-specific immune responses. However, little is known about whether the existence of the protective immune system against MV in the host can exert anti-tumor effects and whether the MV-H gene can serve as a therapeutic gene.

Methods: We first vaccinated mice with measles vaccine, then inoculated them with MV-H protein-expressing tumor cells and observed the rate of tumor formation. We also treated mice with H protein-expressing tumor cells with measles vaccine and assessed tumor size and overall survival.

Results: Active vaccination using measles vaccine not only protected mice from developing tumors, but also eradicated established tumors. Measles vaccine elicited H-specific IFN-γ, TNF-α and granzyme B-producing CD8+ T cells and increased cytotoxic T lymphocyte (CTL) activity specific for H antigen, which provided a strong therapeutic benefit against H protein-expressing tumors. In addition, measles vaccine decreased the population of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs).

Conclusions: Our study demonstrated that tumor cells expressing H protein could activate the immune memory response against MV, which exerted specific anti-tumor effects, and indicated that the MV-H gene can be used as a potential therapeutic gene for cancer gene therapy.

Keywords: Cancer; Cancer immunotherapy; Cytotoxic T lymphocytes; Hemagglutinin; Measles vaccine.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Disease Models, Animal*
  • Hemagglutinins, Viral / genetics
  • Hemagglutinins, Viral / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Measles Vaccine / immunology
  • Measles Vaccine / therapeutic use*
  • Measles virus / immunology*
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Tumor Cells, Cultured
  • Vaccination

Substances

  • Hemagglutinins, Viral
  • Measles Vaccine
  • hemagglutinin protein G, measles virus
  • Interferon-gamma