High-grade, chemotherapy-resistant ovarian carcinomas overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy with MT201, a fully human monoclonal anti-EpCAM antibody

Am J Obstet Gynecol. 2010 Dec;203(6):582.e1-7. doi: 10.1016/j.ajog.2010.07.041. Epub 2010 Sep 25.

Abstract

Objective: We evaluated the expression of epithelial cell adhesion molecule (EpCAM) and the potential of MT201 (adecatumumab), a human-monoclonal-antibody that targets EpCAM against chemotherapy-resistant ovarian disease.

Study design: EpCAM expression was evaluated by real-time polymerase chain reaction and flow cytometry. Sensitivity to MT201 antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in 4-hour chromium-release assays. The effect of interleukin-2 on MT201 ADCC was also studied.

Results: High messenger RNA expression by real-time polymerase chain reaction and high EpCAM surface expression by flow cytometry was detected in 71% of ovarian cancers (5 of 7 cell lines). Although these cell lines were highly resistant to complement-dependent cytotoxicity and natural killer-dependent cytotoxicity in vitro (range of killing, 0-7%), EpCAM-positive cell lines showed high sensitivity to MT201 ADCC (range of killing, 27-66%). Incubation with interleukin-2 further increased the cytotoxic activity against EpCAM-positive ovarian cancer cell lines.

Conclusion: MT201 may represent a novel, potentially highly effective treatment option for patients with ovarian carcinoma whose body is harboring disease refractory to chemotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm / analysis
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism*
  • Cell Adhesion Molecules / pharmacology
  • Cell Line, Tumor / drug effects
  • Drug Resistance, Neoplasm
  • Female
  • Flow Cytometry
  • Humans
  • Immunotherapy / methods*
  • Neoplasm Staging
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology*
  • Ovarian Neoplasms / therapy*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • RNA, Messenger
  • adecatumumab