5 research outputs found
Primary cervical carcinoma cell lines overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy with MT201, a fully human monoclonal anti-EpCAM antibody
Introduction: Epithelial cell adhesion molecule (EpCAM) is a surface glycoprotein
highly differentially expressed in many epithelial malignancies. The goal of this study was
to evaluate the expression of EpCAM and the potential of MT201 (adecatumumab), a
human monoclonal antibody targeting EpCAM, against multiple primary cervical carcinoma
cell lines.
Methods: Epithelial cell adhesion molecule expression was evaluated by real-time polymerase
chain reaction and flow cytometry in a total of 8 primary cervical cancer cell lines.
Sensitivity to MT201-mediated cellular cytotoxicity (ADCC) and complement-dependent
cytotoxicity was tested in standard 4-hour 51Cr release assays. To investigate the effect of
interleukin-2 (IL-2) on MT201-mediated ADCC, 4-hour 51Cr release assays were also
conducted in the presence of low doses of IL-2.
Results: High messenger RNA expression by real-time polymerase chain reaction and
high EpCAM surface expression by flow cytometry were detected in 4 (50%) of 8 primary
cervical carcinoma cell lines. With no exception, the primary cell lines derived from
clinically aggressive tumors showed EpCAM overexpression. Whereas these cell lines were
highly resistant to complement-dependent cytotoxicity and natural killer (NK)-dependent
cytotoxicity in vitro (range of killing, 4%Y19%), EpCAM-positive cell lines showed high
sensitivity to MT201-mediated ADCC (range of killing, 23%Y59%). Incubation with IL-2 in
addition to MT201 significantly increased the cytotoxic activity against EpCAM-positive
cervical cancer cell lines (P = 0.007). Addition of human serum also further increased the
MT201-mediated killing of EpCAM-positive cell lines (P = 0.03).
Conclusions: Epithelial cell adhesion molecule is highly expressed in primary cervical
carcinoma cell lines, and these biologically aggressive tumors are highly sensitive to
MT201-mediated cytotoxicity in vitro. MT201 may represent a novel, potentially highly
effective treatment option for patients with cervical carcinoma, especially for those with
advanced, recurrent, or metastatic disease refractory to standard salvage therapy