Details

Autor(en) / Beteiligte

• Schaefer, Gabriele
• Haber, Lauric
• Crocker, Lisa M.
• Shia, Steven
• Shao, Lily
• Dowbenko, Donald
• Totpal, Klara
• Wong, Anne
• Lee, Chingwei V.
• Stawicki, Scott
• Clark, Robyn
• Fields, Carter
• Lewis Phillips, Gail D.
• Prell, Rodney A.
• Danilenko, Dimitry M.
• Franke, Yvonne
• Stephan, Jean-Philippe
• Hwang, Jiyoung
• Wu, Yan
• Bostrom, Jenny
• Sliwkowski, Mark X.
• Fuh, Germaine
• Eigenbrot, Charles

Titel

A Two-in-One Antibody against HER3 and EGFR Has Superior Inhibitory Activity Compared with Monospecific Antibodies

Ist Teil von

• Cancer cell, 2011-10, Vol.20 (4), p.472-486

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. ► MEHD7945A is a two-in-one antibody that targets EGFR and HER3 ► MEHD7945A epitopes include ligand recognition sites on domain III ► MEHD7945A exhibits superior efficacy over monospecific HER antibodies