Antibody-targeted cell fusion

Takafumi Nakamura, Kah Whye Peng, Sompong Vongpunsawad, Mary Harvey, Hiroyuki Mizuguchi, Takao Hayakawa, Roberto Cattaneo, Stephen J. Russell

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Membrane fusion has many potential applications in biotechnology. Here we show that antibody-targeted cell fusion can be achieved by engineering a fusogenic viral membrane glycoprotein complex. Three different single-chain antibodies were displayed at the extracellular C terminus of the measles hemagglutinin (H) protein, and combinations of point mutations were introduced to ablate its ability to trigger fusion through the native viral receptors CD46 and SLAM. When coexpressed with the measles fusion (F) protein, using plasmid cotransfection or bicistronic adenoviral vectors, the retargeted H proteins could mediate antibody-targeted cell fusion of receptor-negative or receptor-positive index cells with receptor-positive target cells. Adenoviral expression vectors mediating human epidermal growth factor receptor (EGFR)-targeted cell fusion were potently cytotoxic against EGFR-positive tumor cell lines and showed superior antitumor potency against EGFR-positive tumor xenografts as compared with control adenoviruses expressing native (untargeted) or CD38-targeted H proteins.

Original languageEnglish (US)
Pages (from-to)331-336
Number of pages6
JournalNature biotechnology
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2004

ASJC Scopus subject areas

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

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  • Cite this

    Nakamura, T., Peng, K. W., Vongpunsawad, S., Harvey, M., Mizuguchi, H., Hayakawa, T., Cattaneo, R., & Russell, S. J. (2004). Antibody-targeted cell fusion. Nature biotechnology, 22(3), 331-336. https://doi.org/10.1038/nbt942