title: Potent systemic therapy of multiple myeloma utilizing oncolytic vesicular stomatitis virus coding for interferon-β.
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.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: S
authors.initials: S
authors.lastname: Naik
authors.forename: R
authors.initials: R
authors.lastname: Nace
authors.forename: G N
authors.initials: GN
authors.lastname: Barber
authors.forename: S J
authors.initials: SJ
authors.lastname: Russell
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*
chemical_list: D016899:Interferon-beta