Cytotoxic activity of novel human monoclonal antibody MT201 against primary ovarian tumor cells.
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.
Xiang
Wei
W
Department of Gynecology and Obstetrics, University of Munich-Grosshadern, 81377 Munich, Germany.
Wimberger
Pauline
P
Dreier
Torsten
T
Diebold
Joachim
J
Mayr
Doris
D
Baeuerle
Patrick A
PA
Kimmig
Rainer
R
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
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