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

Cancer Gene Therapy volume 19, pages 443–450 (2012)Cite this article

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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.

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Acknowledgements

This work was supported by the Mayo Foundation and NCI grant awards R01CA100634 and R01129966-01, the Richard M. Schulze Family Foundation and a gift from Al and Mary Agnes McQuinn. We thank Dr Ron Marler from the Mayo Clinic Histology Core, Scottsdale, AZ, USA.

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Authors and Affiliations

  1. Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA

    S Naik, R Nace & S J Russell

  2. Department of Medicine and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA

    G N Barber

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  1. S Naik
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Correspondence to S J Russell.

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Naik, S., Nace, R., Barber, G. et al. Potent systemic therapy of multiple myeloma utilizing oncolytic vesicular stomatitis virus coding for interferon-β. Cancer Gene Ther 19, 443–450 (2012). https://doi.org/10.1038/cgt.2012.14

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