Bispecific antibody targeting of doxorubicin to carcinoembryonic antigen-expressing colon cancer cell linesin vitro andin vivo
| Autor: | P.A. Osborne, A. Mathew, C.H.J. Ford, B.G. Rego |
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| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
Time Factors Cell Survival Mice Nude Tetrazolium Salts Antineoplastic Agents Biology Inhibitory Concentration 50 Mice Carcinoembryonic antigen In vivo Antibodies Bispecific Tumor Cells Cultured polycyclic compounds medicine Animals Humans Doxorubicin Viability assay Coloring Agents Dose-Response Relationship Drug Bispecific monoclonal antibody Flow Cytometry Carcinoembryonic Antigen Thiazoles Oncology Cell culture Colonic Neoplasms Immunology Cancer research biology.protein Antibody Oncofetal antigen Neoplasm Transplantation medicine.drug |
| Zdroj: | International Journal of Cancer. 92:851-855 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.1262 |
| Popis: | A bispecific monoclonal antibody (BsMAb) recognising carcinoembryonic antigen (CEA) and doxorubicin (Dox) was used in colorimetric microcytotoxicity assays with 3 human colon cancer cell lines (COLO320DM, SKCO1 and LS174T) showing no, high or medium CEA expression, respectively. The IC50 values for Dox with COLO320DM, SKCO1 and LS174T were 1,163, 28.5 and 324 ng/ml, respectively. BsMAb caused statistically significant reductions in Dox IC50 values at 1, 0.1 and 0.01 μg/ml with the CEA-expressing cell lines SKCO1 and LS174T but not with COLO320DM. BsMAb or control antibody alone had no significant effect on the cell viability of any of the cell lines and did not reduce Dox IC50 values. In vivo, there was a statistically significant inhibition of the growth of CEA-expressing LS174T cells growing as xenografts in nude mice treated with BsMAb and Dox compared to control mice. This effect was not seen with COLO320DM xenografts. Our results demonstrate that a BsMAb that recognises CEA and Dox can reduce the IC50 for Dox in vitro and inhibit growth in vivo in a CEA-specific manner. © 2001 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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