Rescue and propagation of fully retargeted oncolytic measles viruses

Takafumi Nakamura, Kah Whye Peng, Mary Harvey, Suzanne Greiner, Ian A J Lorimer, Charles D. James, Stephen J. Russell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

212 Scopus citations

Abstract

Live attenuated measles viruses of the Edmonston lineage (MV-Edm) have potent anti-tumor activity1-4 but are not entirely tumor-specific owing to widespread distribution of their native receptors, CD465,6 and SLAM7-9. We have therefore developed a pseudoreceptor system that allows rescue and propagation of fully retargeted viruses displaying single-chain antibody fragments. Viruses retargeted to tumor-selective CD38, epidermal growth factor receptor (EGFR) or EGFR mutant vIII (EGFRvIII) efficiently entered cells through their respective targeted receptors in vitro and in vivo, but not through CD46 and SLAM. When administered intratumorally or intravenously to mice bearing human CD38 or EGFR-positive human tumor xenografts, the targeted viruses demonstrated specific receptor-mediated anti-tumor activity. These data provide an in vivo demonstration of antibody-directed tumor destruction by retargeted oncolytic viruses.

Original languageEnglish (US)
Pages (from-to)209-214
Number of pages6
JournalNature biotechnology
Volume23
Issue number2
DOIs
StatePublished - Feb 2005

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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