Sat, 26 Jul 2008 07:36:46 BST CiteULike: msuarezdiez's Chan http://www.citeulike.org/user/msuarezdiez/author/Chan CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/msuarezdiez/article/610244 <i>Proc Natl Acad Sci U S A, Vol. 103, No. 11. (14 March 2006), pp. 4005-4010.</i><br /><br />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. Engineered antibody Fc variants with enhanced effector function. GA Lazar W Dang S Karki O Vafa JS Peng L Hyun C Chan HS Chung A Eivazi SC Yoder J Vielmetter DF Carmichael RJ Hayes BI Dahiyat doi:10.1073/pnas.0508123103 Proc Natl Acad Sci U S A, Vol. 103, No. 11. (14 March 2006), pp. 4005-4010. 2006-05-01T16:44:11-00:00 2006 Proc Natl Acad Sci U S A 0027-8424 103 11 4005 4010 computational_protein_design enzyme_design