Curative one-shot systemic virotherapy in murine myeloma

S. Naik, R. Nace, M. J. Federspiel, G. N. Barber, K. W. Peng, S. J. Russell

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Current therapy for multiple myeloma is complex and prolonged. Antimyeloma drugs are combined in induction, consolidation and/or maintenance protocols to destroy bulky disease, then suppress or eradicate residual disease. Oncolytic viruses have the potential to mediate both tumor debulking and residual disease elimination, but this curative paradigm remains unproven. Here, we engineered an oncolytic vesicular stomatitis virus to minimize its neurotoxicity, enhance induction of antimyeloma immunity and facilitate noninvasive monitoring of its intratumoral spread. Using high-resolution imaging, autoradiography and immunohistochemistry, we demonstrate that the intravenously administered virus extravasates from tumor blood vessels in immunocompetent myeloma-bearing mice, nucleating multiple intratumoral infectious centers that expand rapidly and necrose at their centers, ultimately coalescing to cause extensive tumor destruction. This oncolytic tumor debulking phase lasts only for 72 h after virus administration, and is completed before antiviral antibodies become detectable in the bloodstream. Antimyeloma T cells, cross-primed as the virus-infected cells provoke an antiviral immune response, then eliminate residual uninfected myeloma cells. The study establishes a curative oncolytic paradigm for multiple myeloma where direct tumor debulking and immune eradication of minimal disease are mediated by a single intravenous dose of a single therapeutic agent. Clinical translation is underway.

Original languageEnglish (US)
Pages (from-to)1870-1878
Number of pages9
Issue number8
StatePublished - Aug 2012


  • immunotherapy
  • intravenous
  • multiple myeloma
  • oncolytic virotherapy
  • vesicular stomatitis virus

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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