Uterine serous papillary carcinomas overexpress human trophoblast‐cell‐surface marker (trop‐2) and are highly sensitive to immunotherapy with hRS7, a humanized anti‐trop‐2 monoclonal antibody

Abstract BACKGROUND: Uterine serous papillary carcinoma (USPC) was an aggressive and chemotherapy resistant variant of endometrial cancer. The authors evaluated the expression of human trophoblast‐cell‐surface‐marker (Trop‐2) and the potential of hRS7, a humanized anti‐Trop‐2 monoclonal antibody, as a novel therapeutic strategy against USPC. METHODS: Trop‐2 expression was evaluated by immunohistochemistry (IHC) in a total of 23 USPC. Six primary USPC cell lines were assessed by flow cytometry and real‐time polymerase chain reaction (PCR) for Trop‐2 expression. Sensitivity to hRS7 (Immunomedics, Inc.) antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity was tested in standard 5‐hour 51 Cr‐release assays against primary USPC cell lines. RESULTS: Expression of Trop‐2 was found in 15 of 23 (65%) of the tumor tissues tested by IHC and in 50% (3 of 6) of the USPC cell lines tested by real‐time PCR and flow‐cytometry (Trop‐2 expression in USPC versus normal endometrial cells; P < .005). USPC cell lines overexpressing Trop‐2, regardless of their intrinsic resistance to natural killer cytotoxicity, were highly sensitive to hRS7‐mediated ADCC in vitro (range of killing, 28.2% to 64.4%) ( P < .001). Negligible cytotoxicity against USPC was seen in the absence of hRS7 or in the presence of rituximab control antibody (range of killing, 1.1% to 12.4%). Incubation with interleukin‐2 (50 IU/mL) in addition to hRS7 further increased the cytotoxic activity against USPC cell lines overexpressing Trop‐2 ( P = .008). CONCLUSIONS: Trop‐2 was highly expressed in uterine serous carcinoma at mRNA and protein levels. Primary USPC cell lines are highly sensitivity to hRS7‐mediated cytotoxicity in vitro. hRS7 may represent a novel therapeutic agent for USPC refractory to standard treatment modalities. Cancer 2011. © 2011 American Cancer Society.