Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

Biochem Biophys Res Commun. 2016 Jan 29;470(1):239-244. doi: 10.1016/j.bbrc.2016.01.045. Epub 2016 Jan 11.

Abstract

The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix.

Keywords: Breast cancer; ErbB4; Neuregulin; Neutralizing antibody; Three-dimensional culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cloning, Molecular / methods
  • Drug Design
  • Humans
  • MCF-7 Cells
  • Molecular Targeted Therapy / methods
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / pathology
  • Neuregulin-1 / immunology*
  • Receptor, ErbB-4 / immunology*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • NRG1 protein, human
  • Neuregulin-1
  • ERBB4 protein, human
  • Receptor, ErbB-4