Theiler's murine encephalomyelitis virus as a vaccine candidate for immunotherapy

Kevin D. Pavelko, Megan A. Girtman, Yoshihiro Mitsunaga, Yanice V. Mendez-Fernandez, Michael P. Bell, Michael J. Hansen, Kathleen S. Allen, Moses Rodriguez, Larry R. Pease

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The induction of sterilizing T-cell responses to tumors is a major goal in the development of T-cell vaccines for treating cancer. Although specific components of anti-viral CD8+ immunity are well characterized, we still lack the ability to mimic viral CD8+ T-cell responses in therapeutic settings for treating cancers. Infection with the picornavirus Theiler's murine encephalomyelitis virus (TMEV) induces a strong sterilizing CD8+ T-cell response. In the absence of sterilizing immunity, the virus causes a persistent infection. We capitalized on the ability of TMEV to induce strong cellular immunity even under conditions of immune deficiency by modifying the virus to evaluate its potential as a T-cell vaccine. The introduction of defined CD8+ T-cell epitopes into the leader sequence of the TMEV genome generates an attenuated vaccine strain that can efficiently drive CD8+ T-cell responses to the targeted antigen. This virus activates T-cells in a manner that is capable of inducing targeted tissue damage and glucose dysregulation in an adoptive T-cell transfer model of diabetes mellitus. As a therapeutic vaccine for the treatment of established melanoma, epitope-modified TMEV can induce strong cytotoxic T-cell responses and promote infiltration of the T-cells into established tumors, ultimately leading to a delay in tumor growth and improved survival of vaccinated animals. We propose that epitope-modified TMEV is an excellent candidate for further development as a human T-cell vaccine for use in immunotherapy.

Original languageEnglish (US)
Article numbere20217
JournalPloS one
Volume6
Issue number5
DOIs
StatePublished - May 26 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Pavelko, K. D., Girtman, M. A., Mitsunaga, Y., Mendez-Fernandez, Y. V., Bell, M. P., Hansen, M. J., Allen, K. S., Rodriguez, M., & Pease, L. R. (2011). Theiler's murine encephalomyelitis virus as a vaccine candidate for immunotherapy. PloS one, 6(5), [e20217]. https://doi.org/10.1371/journal.pone.0020217