IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v464y2010i7291d10.1038_nature08878.html
   My bibliography  Save this article

Therapeutic antibody targeting of individual Notch receptors

Author

Listed:
  • Yan Wu

    (Department of Antibody Engineering,)

  • Carol Cain-Hom

    (Department of Molecular Biology,)

  • Lisa Choy

    (Department of Molecular Biology,)

  • Thijs J. Hagenbeek

    (Department of Molecular Biology,)

  • Gladys P. de Leon

    (Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA)

  • Yongmei Chen

    (Department of Antibody Engineering,)

  • David Finkle

    (Department of Translational Oncology,)

  • Rayna Venook

    (Department of Translational Oncology,)

  • Xiumin Wu

    (Department of Tumor Biology and Angiogenesis,)

  • John Ridgway

    (Department of Tumor Biology and Angiogenesis,)

  • Dorreyah Schahin-Reed

    (Department of Neurodegeneration,)

  • Graham J. Dow

    (Department of Molecular Biology,
    Present address: Department of Biology, Stanford University, Stanford, California 94305, USA.)

  • Amy Shelton

    (Department of Molecular Biology,)

  • Scott Stawicki

    (Department of Antibody Engineering,)

  • Ryan J. Watts

    (Department of Neurodegeneration,)

  • Jeff Zhang

    (Exelixis Inc., 210 East Grand Avenue, PO Box 511, South San Francisco, California 94083-0511, USA)

  • Robert Choy

    (Exelixis Inc., 210 East Grand Avenue, PO Box 511, South San Francisco, California 94083-0511, USA)

  • Peter Howard

    (Exelixis Inc., 210 East Grand Avenue, PO Box 511, South San Francisco, California 94083-0511, USA)

  • Lisa Kadyk

    (Exelixis Inc., 210 East Grand Avenue, PO Box 511, South San Francisco, California 94083-0511, USA)

  • Minhong Yan

    (Department of Tumor Biology and Angiogenesis,)

  • Jiping Zha

    (Department of Pathology,)

  • Christopher A. Callahan

    (Department of Pathology,)

  • Sarah G. Hymowitz

    (Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA)

  • Christian W. Siebel

    (Department of Molecular Biology,)

Abstract

Direct action: antitumour potential of Notch receptor antagonists The 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.

Suggested Citation

  • 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 Shelt, 2010. "Therapeutic antibody targeting of individual Notch receptors," Nature, Nature, vol. 464(7291), pages 1052-1057, April.
    • Handle: RePEc:nat:nature:v:464:y:2010:i:7291:d:10.1038_nature08878
    DOI: 10.1038/nature08878
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature08878
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature08878?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Songbai Zhang & Ayako Miyakawa & Malin Wickström & Cecilia Dyberg & Lauri Louhivuori & Manuel Varas-Godoy & Kati Kemppainen & Shigeaki Kanatani & Dagmara Kaczynska & Ivar Dehnisch Ellström & Lotta Elf, 2022. "GIT1 protects against breast cancer growth through negative regulation of Notch," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Wenxue Ma & Alejandro Gutierrez & Daniel J Goff & Ifat Geron & Anil Sadarangani & Christina A M Jamieson & Angela C Court & Alice Y Shih & Qingfei Jiang & Christina C Wu & Kang Li & Kristen M Smith & , 2012. "NOTCH1 Signaling Promotes Human T-Cell Acute Lymphoblastic Leukemia Initiating Cell Regeneration in Supportive Niches," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-14, June.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:464:y:2010:i:7291:d:10.1038_nature08878. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.