Efficient tumor cell lysis by autologous, tumor-resident T lymphocytes in primary ovarian cancer samples by an EP-CAM-/CD3-bispecific antibody.
The epithelial cell adhesion molecule (Ep-CAM) is expressed on the surface of most human carcinomas, including ovarian, breast, lung, prostate and colorectal carcinoma. Ep-CAM was shown to be a valid target for monoclonal antibody-based therapies. We have investigated whether an Ep-CAM-/CD3-bispecific single-chain antibody called bscEp-CAM x CD3 is effective in tumor cell elimination within the cellular microenvironment of primary ovarian cancer tissue. The ex vivo elimination of ovarian cancer cells in tumor preparations from 21 patients was monitored by flow cytometry using Ep-CAM/CA-125 double-labeling or Ep-CAM single-labeling combined with propidium iodide uptake of cells. Methodology was established by the ovarian cancer cell line OvCAR. A total of 17 (81%) patient samples showed a dose-dependent tumor cell elimination by bscEp-CAM x CD3. High and specific tumor cell lysis was seen at bscEp-CAM x CD3 concentrations as low as 1 ng/ml, at very low effector:target ratios and in the absence of T cell costimulation. The high efficacy of the bispecific antibody may be due to the non-restricted activation of tumor-resident cytotoxic T lymphocytes. In clinical trials, the ex vivo data with the T cell-recruiting bispecific antibody bscEp-CAM x CD3 may translate into a high response rate and efficacy of tumor cell elimination.
Wimberger
Pauline
P
Department of Gynecology and Obstetrics, University of Essen, Essen, Germany. pauline.wimberger@med.uni-essen.de
Xiang
Wei
W
Mayr
Doris
D
Diebold
Joachim
J
Dreier
Torsten
T
Baeuerle
Patrick A
PA
Kimmig
Rainer
R
D018033:Antibodies, Bispecific / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000276:immunology / Q000556:secondary*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D011948:Receptors, Antigen, T-Cell