Oncolytic immunovirotherapy for melanoma using vesicular stomatitis virus

Rosa Maria Diaz, Feorillo Galivo, Timothy Kottke, Phonphimon Wongthida, Jian Qiao, Jill Thompson, Mikael Valdes, Glen Barber, Richard G. Vile

Research output: Contribution to journalArticle

201 Scopus citations

Abstract

Relatively little attention has been paid to the role of virotherapy in promoting antitumor immune responses. Here, we show that CD8+ T cells are critical for the efficacy of intratumoral vesicular stomatitis virus virotherapy and are induced against both virally encoded and tumor-associated immunodominant epitopes. We tested three separate immune interventions to increase the frequency/activity of activated antitumoral T cells. Depletion of Treg had a negative therapeutic effect because it relieved suppression of the antiviral immune response, leading to early viral clearance. In contrast, increasing the circulating levels of tumor antigen-specific T cells using adoptive T cell transfer therapy, in combination with intratumoral virotherapy, generated significantly improved therapy over either adoptive therapy or virotherapy alone. Moreover, the incorporation of a tumor-associated antigen within the oncolytic vesicular stomatitis virus increased the levels of activation of naive T cells against the antigen, which translated into increased antitumor therapy. Therefore, our results show that strategies which enhance immune activation against tumor-associated antigens can also be used to enhance the efficacy of virotherapy.

Original languageEnglish (US)
Pages (from-to)2840-2848
Number of pages9
JournalCancer research
Volume67
Issue number6
DOIs
StatePublished - Mar 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Diaz, R. M., Galivo, F., Kottke, T., Wongthida, P., Qiao, J., Thompson, J., Valdes, M., Barber, G., & Vile, R. G. (2007). Oncolytic immunovirotherapy for melanoma using vesicular stomatitis virus. Cancer research, 67(6), 2840-2848. https://doi.org/10.1158/0008-5472.CAN-06-3974