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Cytotoxic activity of novel human monoclonal antibody MT201 against primary ovarian tumor cells

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

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-µg/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.

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Fig. 1A–C.
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Abbreviations

ADCC:

Antibody-dependent cellular cytotoxicity

CDC:

Complement-dependent cytotoxicity

Ep-CAM:

Epithelial cell adhesion molecule

E:T ratio:

Effector to target ratio

FACS:

Fluorescence-activated cell sorting

FBS:

Fetal bovine serum

mAb:

Monoclonal antibodies

PBMC:

Peripheral blood mononuclear cells

PE:

Phycoerythrin

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Acknowledgments

The authors would like to thank Mrs. D. Egner and Mrs. M. Fileki for their technical assistance.

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, University of Munich-Grosshadern, 81377, Munich, Germany

    Wei Xiang

  2. Department of Gynecology and Obstetrics, University of Essen, 45122, Essen, Germany

    Pauline Wimberger & Rainer Kimmig

  3. Micromet, Staffelseestrasse 2, 81477, Munich, Germany

    Torsten Dreier & Patrick A. Baeuerle

  4. Institute of Pathology, University of Munich-Grosshadern, 81377, Munich, Germany

    Joachim Diebold & Doris Mayr

Authors
  1. Wei Xiang
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  2. Pauline Wimberger
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  3. Torsten Dreier
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  4. Joachim Diebold
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  5. Doris Mayr
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  6. Patrick A. Baeuerle
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  7. Rainer Kimmig
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Corresponding author

Correspondence to Pauline Wimberger.

Additional information

The first two authors contributed equally to this study.

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Xiang, W., Wimberger, P., Dreier, T. et al. Cytotoxic activity of novel human monoclonal antibody MT201 against primary ovarian tumor cells. J Cancer Res Clin Oncol 129, 341–348 (2003). https://doi.org/10.1007/s00432-003-0438-6

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  • DOI: https://doi.org/10.1007/s00432-003-0438-6

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