Engineered antibody Fc variants with enhanced effector function.

@article{Lazar2006, 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.}, address = {Xencor, Inc., 111 West Lemon Avenue, Monrovia, CA 91016, USA. glazar@xencor.com}, author = {Lazar, G. A. and Dang, W. and Karki, S. and Vafa, O. and Peng, J. S. and Hyun, L. and Chan, C. and Chung, H. S. and Eivazi, A. and Yoder, S. C. and Vielmetter, J. and Carmichael, D. F. and Hayes, R. J. and Dahiyat, B. I. }, citeulike-article-id = {610244}, doi = {10.1073/pnas.0508123103}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {computational\_protein\_design, enzyme\_design}, month = {March}, number = {11}, pages = {4005--4010}, posted-at = {2008-04-22 11:44:41}, priority = {3}, title = {Engineered antibody Fc variants with enhanced effector function.}, url = {http://dx.doi.org/10.1073/pnas.0508123103}, volume = {103}, year = {2006} }

TY - JOUR ID - Lazar2006 TI - Engineered antibody Fc variants with enhanced effector function. JF - Proc Natl Acad Sci U S A VL - 103 IS - 11 SP - 4005 EP - 4010 AD - Xencor, Inc., 111 West Lemon Avenue, Monrovia, CA 91016, USA. glazar@xencor.com SN - 0027-8424 N2 - 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. KW - computational_protein_design KW - enzyme_design AU - Lazar, GA AU - Dang, W AU - Karki, S AU - Vafa, O AU - Peng, JS AU - Hyun, L AU - Chan, C AU - Chung, HS AU - Eivazi, A AU - Yoder, SC AU - Vielmetter, J AU - Carmichael, DF AU - Hayes, RJ AU - Dahiyat, BI PY - 2006/03/14/ UR - http://dx.doi.org/10.1073/pnas.0508123103 ER -