Shared Antigenic Epitopes and Pathobiological Functions of anti-p185(her2/neu) Monoclonal Antibodies

Exp Mol Pathol. 1999 Sep;67(1):15-25. doi: 10.1006/exmp.1999.2266.

Abstract

We have studied two anti-p185 antibodies: the monoclonal antibody 7. 16.4 and rhuMAb 4D5, which were raised against the the ectodomain of rat (p185(neu)), and the human (p185(her2/neu)) homolog, respectively. Studies on the structure of these two antibodies indicate that they share structural similarity in the variable region, especially the CDR3 region, which determines the antibody-antigen interaction. Further studies by flow cytometry revealed that 7.16.4 can compete with rhuMAb4D5 for binding to the cell surface p185(her2/neu), suggesting that these two antibodies share an epitope on the p185 receptor. Furthermore, 7.16.4 can also inhibit proliferation and transformation caused by p185(her2/neu). Moreover the rhuMAb 4D5 binds to the rat p185(neu). With the observation that 7.16.4 positively stains human breast cancer tissues that overexpress p185(her2/neu), 7.16.4 may be useful for the pathological diagnosis and therapy of human tumors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / physiology*
  • Antibodies, Monoclonal, Humanized
  • Binding Sites, Antibody
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Transformation, Neoplastic
  • Cross Reactions / immunology
  • Epitopes / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoenzyme Techniques
  • Immunoglobulin Variable Region / chemistry
  • Immunoglobulin Variable Region / immunology
  • Male
  • Mice
  • Models, Molecular
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Rats
  • Receptor, ErbB-2 / immunology*
  • Receptor, ErbB-2 / metabolism
  • Tetrazolium Salts / metabolism
  • Thiazoles / metabolism
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Epitopes
  • Immunoglobulin Variable Region
  • Tetrazolium Salts
  • Thiazoles
  • Receptor, ErbB-2
  • thiazolyl blue
  • Trastuzumab