TY - JOUR
T1 - A Two-in-One Antibody against HER3 and EGFR Has Superior Inhibitory Activity Compared with Monospecific Antibodies
AU - Schaefer, Gabriele
AU - Haber, Lauric J.
AU - Crocker, Lisa M.
AU - Shia, Steven
AU - Shao, Lily
AU - Dowbenko, Donald
AU - Tótpál, Klára
AU - Wong, Anne
AU - Lee, Chingwei Vivian
AU - Stawicki, Scott
AU - Clark, Robyn
AU - Fields, Carter
AU - Lewis Phillips, Gail D.
AU - Prell, Rodney A.
AU - Danilenko, Dimitry M.
AU - Franke, Yvonne
AU - Stephan, Jean-Philippe
AU - Hwang, Jiyoung
AU - Wu, Yan
AU - Bostrom, Jenny
AU - Sliwkowski, Mark X.
AU - Fuh, Germaine
AU - Eigenbrot, Charles
PY - 2011/10/18
Y1 - 2011/10/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80054765331&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2011.09.003
DO - 10.1016/j.ccr.2011.09.003
M3 - Article
SN - 1535-6108
VL - 20
SP - 472
EP - 486
JO - CANCER CELL
JF - CANCER CELL
IS - 4
ER -
