title: Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody.
abstract: OBJECTIVE
  We evaluated the expression of human trophoblast cell-surface marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, against treatment-refractory cervical cancer.
  
  
  METHODS
  Trop-2 expression was evaluated by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. Sensitivity to hRS7 antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in 5-hour chromium release assays. The effect of interleukin (IL)-2 on hRS7 ADCC was also investigated.
  
  
  RESULTS
  Membrane Trop-2 expression was observed in 8 of 8 (100%) of the cancer samples tested by immunohistochemistry, but not in normal cervix. High messenger RNA expression by real-time polymerase chain reaction and high Trop-2 surface expression by flow cytometry were detected in 80% of cervical cancers (4 of 5 cell lines). Although these tumors were resistant to natural killer cell-dependent cytotoxicity in vitro (mean killing, 6.0%), Trop-2-positive cell lines showed high sensitivity to hRS7 ADCC (range of killing, 30.6-73.2%). Incubation with IL-2 further increased the level of cytotoxicity against Trop-2-positive tumors.
  
  
  CONCLUSIONS
  hRS7 may represent a novel treatment option for patients with cervical cancer refractory to conventional treatment modalities.
authors: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
authors: Joyce
authors: J
authors: Varughese
authors: Emiliano
authors: E
authors: Cocco
authors: Stefania
authors: S
authors: Bellone
authors: Elena
authors: E
authors: Ratner
authors: Dan-Arin
authors: DA
authors: Silasi
authors: Masoud
authors: M
authors: Azodi
authors: Peter E
authors: PE
authors: Schwartz
authors: Thomas J
authors: TJ
authors: Rutherford
authors: Natalia
authors: N
authors: Buza
authors: Sergio
authors: S
authors: Pecorelli
authors: Alessandro D
authors: AD
authors: Santin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000276:immunology; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D007376:Interleukin-2; C499380:TACSTD2 protein, human; D003165:Complement System Proteins