title: Cytotoxic activity of novel human monoclonal antibody MT201 against primary ovarian tumor cells.
abstract: OBJECTIVE
  The epithelial cell adhesion molecule (Ep-CAM) is a clinically validated target for antibody-based therapy of cancer. The aim of this work was to evaluate the specific cytotoxic activity of a novel fully human Ep-CAM-specific IgG1 antibody, called MT201, against primary ovarian tumor cells and an ovarian tumor cell line.
  
  
  METHODS
  The anti-tumor efficacy of MT201 was examined both in coculture of the ovarian cancer cell line OvCAR-3 and peripheral blood mononuclear cells (PBMCs) from healthy donors, and in primary metastatic tumor specimens freshly dissected from 21 patients with ovarian cancer using only the tumor-resident autologous effector cells. The extent of tumor cell depletion was determined by flow cytometry using Ep-CAM/CA-125 double-labeling or Ep-CAM labeling, both combined with propidium iodide uptake as cell lysis marker.
  
  
  RESULTS
  MT201 at sub- micro g/ml concentrations effectively eliminated OvCar-3 cells in the presence of PBMC. In freshly dissected tumor specimen, endogenous autologous immune cells could lyse, in a MT201-dependent fashion, Ep-CAM-positive tumor cells in 17 out of 21 patients showing an ex vivo response rate of 81%. In certain samples, up to 80% lysis of Ep-CAM-positive tumor cells by MT201 were observed after 16-30 h of incubation.
  
  
  CONCLUSIONS
  These data indicate that MT201 can effectively redirect tumor-resident effector cells against Ep-CAM-positive ovarian cancer cells and may therefore offer an effective therapy for ovarian cancer.
authors.affiliation: Department of Gynecology and Obstetrics, University of Munich-Grosshadern, 81377 Munich, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.forename: Torsten
authors.initials: T
authors.lastname: Dreier
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Baeuerle
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear; D010051:Ovarian Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; C460839:adecatumumab