Cancer Cell
Volume 20, Issue 4, 18 October 2011, Pages 472-486
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Article
A Two-in-One Antibody against HER3 and EGFR Has Superior Inhibitory Activity Compared with Monospecific Antibodies

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Summary

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.

Highlights

► 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

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These authors contributed equally to this work