title: High-grade, chemotherapy-resistant primary ovarian carcinoma cell lines 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, as a therapeutic agent against chemotherapy-resistant ovarian disease.
  
  
  METHODS
  Trop-2 expression was evaluated by immunohistochemistry (IHC) in 50 ovarian serous papillary carcinoma specimens. Trop-2 expression was also evaluated by real-time PCR (qRT-PCR) and flow cytometry in a total of 6 primary ovarian cancer cell lines derived from patients with chemotherapy-resistant disease. Sensitivity to hRS7 antibody-dependent cellular cytotoxicity (ADCC) was tested in standard 5-hour ⁵¹Cr-release assays. The effect of serum and interleukin-2 (IL-2) on hRS7-mediated ADCC was also studied.
  
  
  RESULTS
  Trop-2 expression was found in 41 of 50 (82%) tumor tissues tested by IHC. 83% (5 of 6) of the ovarian cancer cell lines tested by qRT-PCR and flow cytometry demonstrated high Trop-2 expression. All primary ovarian cancer cell lines expressing Trop-2 were highly sensitive to hRS7-mediated ADCC in vitro (range of killing: 19.3% to 40.8%) (p<0.001). Negligible cytotoxicity against chemotherapy-resistant ovarian cancers was seen in the absence of hRS7 or in the presence of rituximab control antibody (range of killing: 1.1% to 8.9%). Human serum did not significantly inhibit hRS7-mediated cytotoxicity while incubation with IL-2 in addition to hRS7 further increased the cytotoxic activity (p=0.04).
  
  
  CONCLUSIONS
  Trop-2 is highly expressed in chemotherapy-resistant ovarian cancer cell lines at mRNA and protein levels. Primary ovarian carcinoma cell lines are highly sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel therapeutic agent for the treatment of high-grade, chemotherapy-resistant ovarian cancer.
authors: Yale University School of Medicine Department of Obstetrics, Gynecology, & Reproductive Sciences, 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: Marta
authors: M
authors: Bellone
authors: Paola
authors: P
authors: Todeschini
authors: Luisa
authors: L
authors: Carrara
authors: Peter E
authors: PE
authors: Schwartz
authors: Thomas J
authors: TJ
authors: Rutherford
authors: Sergio
authors: S
authors: Pecorelli
authors: Alessandro D
authors: AD
authors: Santin
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D007376:Interleukin-2; D012333:RNA, Messenger; C499380:TACSTD2 protein, human