Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody.

Abstract

We evaluated the expression of human trophoblast cell-surface marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, against treatment-refractory cervical cancer. Trop-2 expression was evaluated by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. Sensitivity to hRS7 antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in 5-hour chromium release assays. The effect of interleukin (IL)-2 on hRS7 ADCC was also investigated. Membrane Trop-2 expression was observed in 8 of 8 (100%) of the cancer samples tested by immunohistochemistry, but not in normal cervix. High messenger RNA expression by real-time polymerase chain reaction and high Trop-2 surface expression by flow cytometry were detected in 80% of cervical cancers (4 of 5 cell lines). Although these tumors were resistant to natural killer cell-dependent cytotoxicity in vitro (mean killing, 6.0%), Trop-2-positive cell lines showed high sensitivity to hRS7 ADCC (range of killing, 30.6-73.2%). Incubation with IL-2 further increased the level of cytotoxicity against Trop-2-positive tumors. hRS7 may represent a novel treatment option for patients with cervical cancer refractory to conventional treatment modalities.