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Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7,a humanized anti-Trop-2 antibody
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نویسنده
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raji r. ,guzzo f. ,carrara l. ,varughese j. ,cocco e. ,bellone s. ,betti m. ,todeschini p. ,gasparrini s. ,ratner e. ,silasi d.-a. ,azodi m. ,schwartz p. ,rutherford t.j. ,buza n. ,pecorelli s. ,santin a.d.
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منبع
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journal of experimental and clinical cancer research - 2011 - دوره : 30 - شماره : 1
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چکیده
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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. © 2011 raji et al; licensee biomed central ltd.
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کلیدواژه
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carcinosarcoma; hRS7; immunotherapy; natural killer cell; Trop-2
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آدرس
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department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States, department of pathology,yale university school of medicine,333 cedar street,new haven,ct, United States, division of gynecologic oncology,university of brescia,brescia, Italy, department of obstetrics,gynecology and reproductive sciences,yale university school of medicine,333 cedar street,new haven,ct, United States
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Authors
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