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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-12

AUTHORS

Rhoda Raji, Federica Guzzo, Luisa Carrara, Joyce Varughese, Emiliano Cocco, Stefania Bellone, Marta Betti, Paola Todeschini, Sara Gasparrini, Elena Ratner, Dan-Arin Silasi, Masoud Azodi, Peter Schwartz, Thomas J Rutherford, Natalia Buza, Sergio Pecorelli, Alessandro D Santin

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. More... »

PAGES

106

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1756-9966-30-106

DOI

http://dx.doi.org/10.1186/1756-9966-30-106

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042166716

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22075385


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