title: Trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in HER-2-non-amplified breast cancer cell lines.
abstract: BACKGROUND
  Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by CD56+natural killer (NK) cells may contribute to the activity of trastuzumab in HER-2-amplified tumours. In this study, we investigated the possibility that trastuzumab might induce ADCC against HER-2-non-amplified breast cancer cells.
  
  
  METHODS
  Induction of NK cell-mediated ADCC was examined in trastuzumab-treated HER-2-non-amplified breast cancer cell lines. HER-2 protein levels were also determined in tumour and autologous normal tissue samples from patients with HER-2 negative breast cancer.
  
  
  RESULTS
  Trastuzumab induced a significant ADCC response in the HER-2-amplified HCC1954 and SKBR3 cell lines, and in all five of the non-amplified cell lines, which had low levels of detectable HER-2 by western blot (CAL-51, CAMA-1, MCF-7, T47D, and EFM19). Trastuzumab did not induce ADCC in the K562 control cell line or MDA-MB-468, which has very low levels of HER-2 detectable by enzyme-linked immunosorbent assay (ELISA) only. HER-2 protein was detected by ELISA in 14/15 patient tumour samples classified as HER-2-non-amplified. Significantly lower levels of HER-2 were detected in normal autologous tissue compared with tumour samples from the same patients.
  
  
  CONCLUSIONS
  Our results suggest that HER-2-non-amplified breast cancer cells, with low but detectable levels of HER-2 protein, can bind trastuzumab and initiate ADCC.
authors: Molecular Therapeutics for Cancer Ireland (MTCI), National Institute for Cellular Biotechnology (NICB), Dublin City University, and Department of Pathology and Laboratory Medicine, St. Vincent's University Hospital, Dublin, Ireland. denis.collins@dcu.ie
authors: D M
authors: DM
authors: Collins
authors: N
authors: N
authors: O'Donovan
authors: P M
authors: PM
authors: McGowan
authors: F
authors: F
authors: O'Sullivan
authors: M J
authors: MJ
authors: Duffy
authors: J
authors: J
authors: Crown
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000378:metabolism / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human