Purpose: 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.