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Cancer Cell. 2011 Oct 18;20(4):472-86. doi: 10.1016/j.ccr.2011.09.003.

A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies.

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Department of Research Oncology, Genentech, Inc, South San Francisco, CA 94080, USA.


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.

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