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Nature Biotechnology  23, 209 - 214 (2005)
Published online: 30 January 2005; | doi:10.1038/nbt1060

Rescue and propagation of fully retargeted oncolytic measles viruses

Takafumi Nakamura1, Kah-Whye Peng1, Mary Harvey1, Suzanne Greiner1, Ian A J Lorimer2, Charles D James3 & Stephen J Russell1

1  Molecular Medicine Program, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, Minnesota 55905, USA.

2  Ottawa Health Research Institute, University of Ottawa, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.

3  Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, Minnesota 55905, USA.

Correspondence should be addressed to Stephen J Russell sjr@mayo.edu
Live attenuated measles viruses of the Edmonston lineage (MV-Edm) have potent anti-tumor activity1, 2, 3, 4 but are not entirely tumor-specific owing to widespread distribution of their native receptors, CD465, 6 and SLAM7, 8, 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.


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Nature Biotechnology
ISSN: 1087-0156
EISSN: 1546-1696
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