3P11

anti-EGFR/HER3 Fab DL11 in complex with domains I-III of the HER3 extracellular region

Summary for 3P11

• Entry DOI: 10.2210/pdb3p11/pdb
• Related: 3P0V 3P0Y
• Descriptor: Fab DL11 heavy chain, Fab DL11 light chain, Receptor tyrosine-protein kinase erbB-3, ... (5 entities in total)
• Functional Keywords: beta-sandwich, antigens her3, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 106133.06

Authors

Eigenbrot, C.,Shia, S. (deposition date: 2010-09-29, release date: 2011-10-26, Last modification date: 2024-11-06)

Primary citation

Schaefer, G.,Haber, L.,Crocker, L.M.,Shia, S.,Shao, L.,Dowbenko, D.,Totpal, K.,Wong, A.,Lee, C.V.,Stawicki, S.,Clark, R.,Fields, C.,Lewis Phillips, G.D.,Prell, R.A.,Danilenko, D.M.,Franke, Y.,Stephan, J.P.,Hwang, J.,Wu, Y.,Bostrom, J.,Sliwkowski, M.X.,Fuh, G.,Eigenbrot, C.
A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies.
Cancer Cell, 20:472-486, 2011

PubMed 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.

PubMed: 22014573
DOI: 10.1016/j.ccr.2011.09.003

Experimental method

X-RAY DIFFRACTION (3.7 Å)