| Literature DB >> 22014573 |
Gabriele Schaefer1, Lauric Haber, Lisa M Crocker, Steven Shia, Lily Shao, Donald Dowbenko, Klara Totpal, Anne Wong, Chingwei V Lee, Scott Stawicki, Robyn Clark, Carter Fields, Gail D Lewis Phillips, Rodney A Prell, Dimitry M Danilenko, Yvonne Franke, Jean-Philippe Stephan, Jiyoung Hwang, Yan Wu, Jenny Bostrom, Mark X Sliwkowski, Germaine Fuh, Charles Eigenbrot.
Abstract
Extensive crosstalk among ErbB/HER receptors suggests that blocking signaling from more than one family member may be essential to effectively treat cancer and limit drug resistance. We generated a conventional IgG molecule MEHD7945A with dual HER3/EGFR specificity by phage display engineering and used structural and mutational studies to understand how a single antigen recognition surface binds two epitopes with high affinity. As a human IgG1, MEHD7945A exhibited dual action by inhibiting EGFR- and HER3-mediated signaling in vitro and in vivo and the ability to engage immune effector functions. Compared with monospecific anti-HER antibodies, MEHD7945A was more broadly efficacious in multiple tumor models, showing that combined inhibition of EGFR and HER3 with a single antibody is beneficial.Entities:
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Year: 2011 PMID： 22014573 DOI： 10.1016/j.ccr.2011.09.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743