Potent systemic therapy of multiple myeloma utilizing oncolytic vesicular stomatitis virus coding for interferon-Β

S. Naik, R. Nace, G. N. Barber, S. J. Russell

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Multiple myeloma (MM) is an incurable malignancy of plasma secreting B cells disseminated in the bone marrow. Successful utilization of oncolytic virotherapy for myeloma treatment requires a systemically administered virus that selectively destroys disseminated myeloma cells in an immune-competent host. Vesicular stomatitis virus (VSV)-expressing interferon-Β (IFNΒ) is a promising new oncolytic agent that exploits tumor-associated defects in innate immune signaling pathways to destroy cancer cells specifically. We demonstrate here that a single, intravenous dose of VSV coding for IFNΒ (VSV-IFNΒ) specifically destroys subcutaneous and disseminated 5TGM1 myeloma in an immune-competent myeloma model. VSV-IFN treatment significantly prolonged survival in mice bearing orthotopic myeloma. Viral murine IFNΒ expression further delayed myeloma progression and significantly enhanced survival compared with VSV-expressing human IFNΒ. Evaluation of VSV-IFNΒ oncolytic activity in human myeloma cell lines and primary patient samples confirmed myeloma-specific oncolytic activity, but revealed variable susceptibility to VSV-IFNΒ oncolysis. The results indicate that VSV-IFNΒ is a potent, safe oncolytic agent that can be systemically administered to target and destroy disseminated myeloma effectively in immune-competent mice. IFNΒ expression improves cancer specificity and enhances VSV therapeutic efficacy against disseminated myeloma. These data show VSV-IFNΒ to be a promising vector for further development as a potential therapy for the treatment of MM.

Original languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalCancer gene therapy
Volume19
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • myeloma
  • oncolytic
  • systemic
  • vesicular stomatitis virus
  • virotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

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