Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes

Oncogene. 2008 Jun 19;27(27):3870-4. doi: 10.1038/onc.2008.13. Epub 2008 Feb 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal / metabolism*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Binding Sites, Antibody
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology
  • Drug Synergism
  • ErbB Receptors / immunology*
  • Female
  • Humans
  • Receptor, ErbB-2 / drug effects
  • Receptor, ErbB-2 / immunology*
  • Receptor, ErbB-3 / immunology*

Substances

  • 2C4 antibody
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • pertuzumab