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
| Autor: | Alessandro D. Santin, Emiliano Cocco, Thomas J. Rutherford, Joyce Varughese, Luisa Carrara, Peter E. Schwartz, Paola Todeschini, Sergio Pecorelli, Stefania Bellone, Marta Bellone |
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| Rok vydání: | 2011 |
| Předmět: |
Antibodies
Monoclonal Antibody-Dependent Cell Cytotoxicity Antigens Neoplasm Cell Adhesion Molecules Cell Line Tumor Drug Resistance Neoplasm Female Flow Cytometry Humans Immunoglobulin G Immunohistochemistry Interleukin-2 Killer Cells Natural Middle Aged Molecular Targeted Therapy Ovarian Neoplasms RNA Messenger medicine.medical_treatment Messenger Drug Resistance Antibodies Article Cell Line Flow cytometry Ovarian disease Ovarian carcinoma Monoclonal Killer Cells Medicine Antigens Antibody-dependent cell-mediated cytotoxicity Tumor biology medicine.diagnostic_test business.industry Obstetrics and Gynecology Immunotherapy medicine.disease Molecular biology Oncology Natural biology.protein Neoplasm RNA Antibody business Ovarian cancer |
| Zdroj: | Gynecologic Oncology. 122:171-177 |
| ISSN: | 0090-8258 |
| Popis: | 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.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.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%) (p0.001). 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).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. |
| Databáze: | OpenAIRE |
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