Journal
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
Volume 203, Issue 6, Pages -Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.ajog.2010.07.041
Keywords
adecatumumab; chemotherapy; cytotoxicity; EpCAM; monoclonal antibody; MT201; natural killer cell; ovarian cancer
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Funding
- Angelo Novicelli Foundation
- Camillo Golgi Foundation, Brescia, Italy
- National Institutes of Health [R01 CA122728-01A2]
- Italian Institute of Health [501/A3/3, 00227557]
- National Cancer Institute, National Institutes of Health [CA-16359]
- Berlucchi Foundation
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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.
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