Maraba virus as a potent oncolytic vaccine vector

Mol Ther. 2014 Feb;22(2):420-429. doi: 10.1038/mt.2013.249. Epub 2013 Oct 25.

Abstract

The rhabdovirus Maraba has recently been characterized as a potent oncolytic virus. In the present study, we engineered an attenuated Maraba strain, defined as MG1, to express a melanoma-associated tumor antigen. Its ability to mount an antitumor immunity was evaluated in tumor-free and melanoma tumor-bearing mice. Alone, the MG1 vaccine appeared insufficient to prime detectable adaptive immunity against the tumor antigen. However, when used as a boosting vector in a heterologous prime-boost regimen, MG1 vaccine rapidly generated strong antigen-specific T-cell immune responses. Once applied for treating syngeneic murine melanoma tumors, our oncolytic prime-boost vaccination protocol involving Maraba MG1 dramatically extended median survival and allowed complete remission in more than 20% of the animals treated. This work describes Maraba virus MG1 as a potent vaccine vector for cancer immunotherapy displaying both oncolytic activity and a remarkable ability to boost adaptive antitumor immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology
  • Cytopathogenic Effect, Viral
  • Female
  • Gene Expression
  • Genetic Vectors / genetics*
  • Genetic Vectors / immunology
  • Immunization, Secondary / methods
  • Intramolecular Oxidoreductases / genetics
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Melanoma, Experimental
  • Mice
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Oncolytic Viruses / genetics*
  • Oncolytic Viruses / immunology
  • Rhabdoviridae / genetics*
  • Rhabdoviridae / immunology
  • Treatment Outcome
  • Vesiculovirus / genetics
  • Vesiculovirus / immunology
  • Viral Tropism

Substances

  • Cancer Vaccines
  • Intramolecular Oxidoreductases
  • dopachrome isomerase