Infected cell carriers: A new strategy for systemic delivery of oncolytic measles viruses in cancer virotherapy

Ianko D. Iankov, Boris Blechacz, Chunsheng Liu, Jeffrey D. Schmeckpeper, James E. Tarara, Mark J. Federspiel, Noel Caplice, Stephen J. Russell

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

Attenuated measles viruses (MVs) propagate selectively in human tumor cells, and phase I clinical trials are currently underway to test their oncolytic activity. A major theoretical impediment to systemic MV application is the presence of pre-existing antiviral immunity. We hypothesized that autologous MV-infected cells might be a more reliable vehicle than cell-free virions to deliver the infection to tumor cells in subjects with neutralizing titers of anti-measles antibodies. Our in vitro studies, using a dual-color fluorescent model, demonstrated efficient cell-to-cell transfer of infection via heterofusion. In contrast to infection by naked virions, heterofusion between infected cell carriers and tumor cells was more resistant to antibody neutralization. Infected monocytic, endothelial, or stimulated peripheral blood cells could deliver oncolytic MV to tumor lesions in vivo, after intravenous (i.v.) or intraperitoneal (i.p.) administration. Single or repeated i.p. injections of monocytic carriers significantly improved survival of animals bearing human ovarian cancer xenografts. Systemic or i.p. injection of MV-infected cells successfully transferred infection by heterofusion to Raji lymphomas or hepatocellular carcinoma tumors in the presence of neutralizing antibodies. These results suggest a novel strategy for systemic delivery of oncolytic virotherapy in cancer patients that can "bypass" the pre-existing humoral immunity against MV.

Original languageEnglish (US)
Pages (from-to)114-122
Number of pages9
JournalMolecular Therapy
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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