Therapeutic antibody targeting of individual Notch receptors View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-04

AUTHORS

Yan Wu, Carol Cain-Hom, Lisa Choy, Thijs J. Hagenbeek, Gladys P. de Leon, Yongmei Chen, David Finkle, Rayna Venook, Xiumin Wu, John Ridgway, Dorreyah Schahin-Reed, Graham J. Dow, Amy Shelton, Scott Stawicki, Ryan J. Watts, Jeff Zhang, Robert Choy, Peter Howard, Lisa Kadyk, Minhong Yan, Jiping Zha, Christopher A. Callahan, Sarah G. Hymowitz, Christian W. Siebel

ABSTRACT

Direct action: antitumour potential of Notch receptor antagonistsThe four receptors of the Notch family are widely expressed transmembrane proteins through which mammalian cells communicate to regulate cell fate and growth. Defects in Notch signalling are linked to many cancers, including acute lymphoblastic leukaemia. Using phage display technology, a multi-department team at Genentech has produced synthetic antibodies that act as potent and specific antagonists of Notch1 and Notch2. Anti-Notch1 shows antitumour activity in pre-clinical mouse models, inhibiting both cancer cell growth and angiogenesis, and is active against human cancer cells in culture. Inhibition of Notch1 and 2 together causes intestinal toxicity, whereas inhibition of each singly largely avoids this effect, a potential therapeutic advantage over 'pan-Notch' inhibitors. More... »

PAGES

1052-1057

Journal

TITLE

Nature

ISSUE

7291

VOLUME

464

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature08878

    DOI

    http://dx.doi.org/10.1038/nature08878

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1026135489

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20393564


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