Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody

Abstract

BackgroundWe evaluated the expression of human trophoblastic cell-surface marker (Trop-2) and the potential of hRS7 - a humanized monoclonal anti-Trop-2 antibody - as a therapeutic strategy against treatment-refractory human uterine (UMMT) and ovarian (OMMT) carcinosarcoma cell lines.Materials and methodsTrop-2 expression was evaluated by immunohistochemistry (IHC) in paraffin-embedded tumor tissues, by real-time polymerase-chain-reaction (RT-PCR) and flow-cytometry in cell lines. Sensitivity to hRS7 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested using 5-hour chromium-release assays against UMMT and OMMT cells.ResultsTrop-2 expression was elevated in 9 of 26 (35%) UMMT and 8 of 14 (57%) OMMT tissues tested by IHC. Positivity for Trop-2 mRNA by RT-PCR and surface expression by flow cytometry were detected in 2 of 4 cell lines, with high positivity noted in OMMT-ARK-2. OMMT-ARK-2 was highly sensitive to hRS7 ADCC (range: 34.7-41.0%; P < 0.001) with negligible cytotoxicity seen in the absence of hRS7 or in the presence of control antibody (range: 1.1-2.5%). Human IgG did not significantly inhibit ADCC while human complement increased, hRS7-mediated-cytotoxicity against OMMT-ARK-2.ConclusionTrop-2 is overexpressed in a proportion of UMMT and OMMT, and hRS7 may represent a novel, potentially highly effective treatment option for patients with treatment-refractory carcinosarcomas overexpressing Trop-2.

TROP‐2 expression in papillary thyroid cancer: a preliminary cyto‐histological study

“…Several authors have claimed its involvement in tumour invasion and metastasis, as it is correlated with a poor prognosis, probably increasing tumour cell resistance to apoptosis . More recent reports have also hypothesized a potential role of TROP‐2 as a target for immunotherapy . These data suggest a potential role of TROP‐2 overexpression in cancer development, and as a prognostic and predictive factor in thyroid cancer.…”

Trop2 and its overexpression in cancers: regulation and clinical/ therapeutic implications

“…hRS7 is a humanized monoclonal anti-Trop2 antibody that can act as an inhibitor of cancer cell lines (OMMT, UMMT, EEC) and refractory cervical carcinoma [ 2 , 67 , 68 ]. Numerous hRS7 conjugate drugs also exist [ 69 ].…”

Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma

“…Trop-2 was originally identified in human trophoblasts [13] and has been shown to be upregulated in a variety of human carcinomas [14-20]. Importantly, overexpression relative to normal tissue has been documented in ovarian, endometrial, and cervical cancers across a broad range of histologies including papillary serous [21-23] and endometrioid [24] adenocarcinomas, squamous cell carcinomas [25] and carcinosarcomas [26]. …”