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Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4005-10. Epub 2006 Mar 6.

Engineered antibody Fc variants with enhanced effector function.

Author information

  • 1Xencor, Inc., 111 West Lemon Avenue, Monrovia, CA 91016, USA. glazar@xencor.com

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 Fcgamma 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 Fcgamma 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.

PMID:
16537476
[PubMed - indexed for MEDLINE]
PMCID:
PMC1389705
Free PMC Article
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