EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201) in chemotherapy-resistant ovarian cancer cell lines.

Abstract

e15524 Background: To evaluate the expression of epithelial cell adhesion molecule (EpCAM) and to determine the cytotoxic potential of MT201 (adecatumumab), a fully human recombinant IgG1 anti-EpCAM antibody, against multiple primary chemotherapy- resistant ovarian cancer cell lines in vitro. Methods: EpCAM expression was evaluated by real time-PCR and flow cytometry in a total of seven primary ovarian cancer cell lines established from patients who showed disease progression on multiple chemotherapeutic regimens. Sensitivity to MT201 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) was tested in these primary ovarian cancer cell lines expressing different levels of EpCAM in standard 5-hour 51Cr assays. To investigate the effect of interleukin-2 (IL-2) on MT201-mediated ADCC, 5-hour 51Cr assays were also conducted after stimulation with low doses of IL-2. Results: Five papillary-serous and two clear cell ovarian carcinoma cell lines were evaluated. High EpCAM surface expression by flow cytometry and high mRNA expression by real time-PCR was detected in 71% of primary ovarian cancer cell lines (five out of seven cell lines). While these cell lines were highly resistant to CDC and natural killer dependent cytotoxicity in vitro (range of killing 0% to 7%), EpCAM-positive cell lines showed very high sensitivity to MT201-mediated ADCC (range of killing 27% to 66%). Incubation with IL-2 in addition to MT201 significantly increased the cytotoxic activity against EpCAM-positive ovarian cancer cell lines (p < 0.0001). Conclusions: EpCAM is highly expressed in primary chemotherapy- resistant ovarian carcinoma cell lines, and these chemotherapy-resistant tumors are highly sensitive to MT201-mediated cytotoxicity in vitro. MT201 may represent a novel, potentially highly effective treatment option for patients harboring chemotherapy-resistant ovarian carcinoma. No significant financial relationships to disclose.