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

BELLONE, Stefania;PECORELLI, Sergio;
2011-01-01
2011
Nessuno
LS7_7 Surgery
LS7_6 Gene therapy, stem cell therapy, regenerative medicine
LS7_9 Health services, health care research
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
Inglese
2011 Nov 10
30
106
ABSTRACT: BACKGROUND: We 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 METHODS: Trop-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. RESULTS: Trop-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. CONCLUSION: Trop-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.
carcinoma; trop-2
17
info:eu-repo/semantics/article
262
Raji, R; Guzzo, F; Carrara, L; Varughese, J; Cocco, E; Bellone, Stefania; Betti, M; Todeschini, P; Gasparrini, S; Ratner, E; Silasi, Da; Azodi, M; Sch...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11379/112914
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