Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes.
2C4 (Pertuzumab, Omnitarg) is a monoclonal antibody targeting p185(her2/neu), which is overexpressed in 30% of invasive breast cancer. 2C4 is currently in phase II clinical trials for several types of cancers. This antibody has been reported to disrupt the association between p185(her2/neu) and ErbB3. In our studies of epidermal growth factor receptor (EGFR)-p185(her2/neu) heterodimerization, we noted that 2C4 formed associations with the EGFR-p185(her2/neu) receptor complex. Our data argue against 2C4 as a universal heterodimerization blocker for p185(her2/neu), but indicate that cocktails of monoclonal antibodies binding distinct interaction surfaces of p185(her2/neu) will emerge as the most potent targeted therapy.
Cai
Z
Z
Department of Pathology/Lab Medicine, University of Pennsylvania School of Medicine, Hamilton Walk, Philadelphia, PA 19104, USA.
Zhang
G
G
Zhou
Z
Z
Bembas
K
K
Drebin
J A
JA
Greene
M I
MI
Zhang
H
H
D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001666:Binding Sites, Antibody; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology; D004357:Drug Synergism; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000276:immunology*; D020893:Receptor, ErbB-3 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C481039:2C4 antibody; C485206:pertuzumab