Growth inhibition of breast cancer cell lines overexpressing Her2/neu by a novel internalized fully human Fab antibody fragment

Cancer Immunol Immunother. 2006 Sep;55(9):1091-9. doi: 10.1007/s00262-005-0100-z. Epub 2005 Nov 26.


The Her2/neu oncogene is overexpressed in various human cancers of epithelial origin and is associated with increased metastatic potential and poor prognosis. Blocking the Her2/neu signalling has been the focus of most therapeutic approaches. In this paper, the Her2/neu extracellular domain expressed in soluble form in yeast Pichia pastoris was used in order to isolate a fully human Fab fragment from a combinatorial Fab phage display library, derived from invaded lymph nodes of a breast cancer patient. The isolated fully human Fab63 binds specifically the native Her2/neu receptor and competes with Herceptin for binding to soluble Her2/neu receptor. In Her2/neu overexpressing cancer cells, Fab63 is rapidly internalized and has significant antiproliferative effects, where ligand-independent mechanisms dominate signal induction. Moreover, in the presence of the ligand heregulin, growth inhibition was also detected by Fab63. The human Fab63 is a non-immunogenic agent with unique properties that can be applied in diagnosis and cancer therapy, with great potential for further manipulation towards the generation of an effective anticancer molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Antibody Specificity
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin Fab Fragments / immunology*
  • Immunoglobulin Fab Fragments / isolation & purification
  • Immunoglobulin Fab Fragments / pharmacology
  • Microscopy, Confocal
  • Peptide Library*
  • Pichia / chemistry
  • Pichia / genetics
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Trastuzumab
  • Up-Regulation


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Immunoglobulin Fab Fragments
  • Peptide Library
  • Receptor, ErbB-2
  • Trastuzumab