Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Engineered Antibody Fc Variants with Enhanced Effector Function

Greg A. Lazar, Wei Dang, Sher Karki, Omid Vafa, Judy S. Peng, Linus Hyun, Cheryl Chan, Helen S. Chung, Araz Eivazi, Sean C. Yoder, Jost Vielmetter, David F. Carmichael, Robert J. Hayes and Bassil I. Dahiyat
Proceedings of the National Academy of Sciences of the United States of America
Vol. 103, No. 11 (Mar. 14, 2006), pp. 4005-4010
Stable URL: http://www.jstor.org/stable/30048873
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Engineered Antibody Fc Variants with Enhanced Effector Function
Preview not available

Abstract

Antibody-dependent cell-mediated cytotoxicity, a key effector function for the clinical efficacy of monoclonal antibodies, is mediated primarily through a set of closely related Fcγ receptors with both activating and inhibitory activities. By using computational design algorithms and high-throughput screening, we have engineered a series of Fc variants with optimized Fcγ receptor affinity and specificity. The designed variants display >2 orders of magnitude enhancement of in vitro effector function, enable efficacy against cells expressing low levels of target antigen, and result in increased cytotoxicity in an in vivo preclinical model. Our engineered Fc regions offer a means for improving the next generation of therapeutic antibodies and have the potential to broaden the diversity of antigens that can be targeted for antibody-based tumor therapy.

Page Thumbnails

  • Thumbnail: Page 
4005
    4005
  • Thumbnail: Page 
4006
    4006
  • Thumbnail: Page 
4007
    4007
  • Thumbnail: Page 
4008
    4008
  • Thumbnail: Page 
4009
    4009
  • Thumbnail: Page 
4010
    4010