title: Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Raji
authors.forename: Federica
authors.initials: F
authors.lastname: Guzzo
authors.forename: Luisa
authors.initials: L
authors.lastname: Carrara
authors.forename: Joyce
authors.initials: J
authors.lastname: Varughese
authors.forename: Emiliano
authors.initials: E
authors.lastname: Cocco
authors.forename: Stefania
authors.initials: S
authors.lastname: Bellone
authors.forename: Marta
authors.initials: M
authors.lastname: Betti
authors.forename: Paola
authors.initials: P
authors.lastname: Todeschini
authors.forename: Sara
authors.initials: S
authors.lastname: Gasparrini
authors.forename: Elena
authors.initials: E
authors.lastname: Ratner
authors.forename: Dan-Arin
authors.initials: DA
authors.lastname: Silasi
authors.forename: Masoud
authors.initials: M
authors.lastname: Azodi
authors.forename: Peter
authors.initials: P
authors.lastname: Schwartz
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rutherford
authors.forename: Natalia
authors.initials: N
authors.lastname: Buza
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002296:Carcinosarcoma / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism*; D014599:Uterus
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; C499380:TACSTD2 protein, human; D003165:Complement System Proteins
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