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

doi:10.1038/nbt1060

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

Molecular Medicine

Research output: Contribution to journal › Article › peer-review

212 Scopus citations

Abstract

Live attenuated measles viruses of the Edmonston lineage (MV-Edm) have potent anti-tumor activity^1-4 but are not entirely tumor-specific owing to widespread distribution of their native receptors, CD46^5,6 and SLAM^7-9. 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 language	English (US)
Pages (from-to)	209-214
Number of pages	6
Journal	Nature biotechnology
Volume	23
Issue number	2
DOIs	https://doi.org/10.1038/nbt1060
State	Published - Feb 2005

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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title = "Rescue and propagation of fully retargeted oncolytic measles viruses",

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.",

author = "Takafumi Nakamura and Peng, {Kah Whye} and Mary Harvey and Suzanne Greiner and Lorimer, {Ian A.J.} and James, {Charles D.} and Russell, {Stephen J.}",

note = "Funding Information: We thank A. Pl{\"u}ckthun for the generous gift of His scFv, J.A. Lust for CD38 scFv, G. Winter for EGFR scFv, J.P. Atkinson for CD46 plasmid, Y. Yanagi for CHO-SLAM cells and E. Vitetta for SKOV3ip.1 cells. This study is supported by the Mayo Foundation, Harold W. Siebens Foundation and National Institutes of Health grants CA100634-01.",

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doi = "10.1038/nbt1060",

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AU - Nakamura, Takafumi

AU - Peng, Kah Whye

AU - Harvey, Mary

AU - Greiner, Suzanne

AU - Lorimer, Ian A.J.

AU - James, Charles D.

AU - Russell, Stephen J.

N1 - Funding Information: We thank A. Plückthun for the generous gift of His scFv, J.A. Lust for CD38 scFv, G. Winter for EGFR scFv, J.P. Atkinson for CD46 plasmid, Y. Yanagi for CHO-SLAM cells and E. Vitetta for SKOV3ip.1 cells. This study is supported by the Mayo Foundation, Harold W. Siebens Foundation and National Institutes of Health grants CA100634-01.

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Rescue and propagation of fully retargeted oncolytic measles viruses

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