Cellular and complement-dependent cytotoxicity of Ep-CAM-specific monoclonal antibody MT201 against breast cancer cell lines
| Autor: | A J da Silva, Klaus Brischwein, Nadja Prang, Carola Steiger, Patrick A. Baeuerle, A Wöppel, P Göster, J Müller, Susanne Preithner, M Peters |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
medicine.drug_class Receptor ErbB-2 Breast Neoplasms Monoclonal antibody Antibodies Monoclonal Humanized chemistry.chemical_compound MT201 breast cancer Trastuzumab Antigens Neoplasm Cell Line Tumor medicine Animals Humans Complement Activation Molecular Diagnostics Antibody-dependent cell-mediated cytotoxicity biology Ep-CAM Cell adhesion molecule Antibody-Dependent Cell Cytotoxicity Antibodies Monoclonal Epithelial cell adhesion molecule Epithelial Cell Adhesion Molecule Complement-dependent cytotoxicity Oncology chemistry Monoclonal Immunology biology.protein Cancer research Antibody ADCC Cell Adhesion Molecules CDC medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 0007-0920 |
| Popis: | MT201 is a fully human monoclonal IgG1 antibody with moderate affinity for epithelial cell adhesion molecule (Ep-CAM) being clinically developed for the treatment of carcinomas. Like many other clinically validated IgG1 monoclonal antibodies, MT201 primarily acts by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Here, we analysed ADCC and CDC induced by MT201 and, as reference, trastuzumab against a panel of nine human breast cancer cell lines expressing distinct surface levels of Ep-CAM and human epithelial growth factor receptor type 2 antigen. Maximal cell lysis by ADCC by MT201 and trastuzumab in the presence of peripheral mononuclear cells did not significantly differ when averaged over the nine cell lines, but showed marked differences with respect to individual cell lines. The extent of cell lysis at intermediate surface target density was highly variable, suggesting a dominant influence of other susceptibility factors. Only one breast cancer cell line was eliminated via CDC, but only by MT201. Resistance to CDC appeared to correlate with high expression levels of complement resistance factors. Our present data as well as recent data on the prevalence and prognostic relevance of Ep-CAM expression in metastatic breast cancer suggest that Ep-CAM-specific monoclonal IgG1 antibodies may have a significant therapeutic potential in the treatment of breast cancer. |
| Databáze: | OpenAIRE |
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