Human monoclonal antibodies to the insulin-like growth factor 1 receptor inhibit receptor activation and tumor growth in preclinical studies
| Autor: | Wen-Rong Lie, Pegg Jodi Ann, J. Alan Arbuckle, John Elvin, Mark Moffat, Tristan J. Vaughan, Simon N Lennard, Debra M. Meyer, Duo Sun, Michelle L. Evans, Christine E. Smith, Peter J. Nicastro, Gerald Fries Casperson, Karen S. Bailey, Phillip A. Morton, Herbert A. Runnels, Christine P. Bono |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.drug_class
medicine.medical_treatment Antibody Affinity Down-Regulation Mice Nude Biology Monoclonal antibody Transfection Receptor IGF Type 1 chemistry.chemical_compound Insulin-like growth factor Mice Downregulation and upregulation In vivo Cell Line Tumor medicine Tumor Cells Cultured Animals Humans Pharmacology (medical) Growth factor receptor inhibitor Receptor Cell Proliferation Dose-Response Relationship Drug Growth factor Antibodies Monoclonal General Medicine 3T3 Cells Molecular biology Figitumumab chemistry Cancer research Epitope Mapping Signal Transduction |
| Zdroj: | Advances in therapy. 27(7) |
| ISSN: | 1865-8652 |
| Popis: | The insulin-like growth factor type 1 (IGF-1) receptor contributes importantly to transformation and survival of tumor cells both in vitro and in vivo, and selective antagonists of the IGF-1 receptor (IGF-1R) activity represent an attractive experimental approach for human cancer therapy.Using a phage display library, we identified several high-affinity fully human monoclonal antibodies with inhibitory activity against both human and rodent IGF.1Rs.These candidate therapeutic antibodies recognized several distinct epitopes and effectively blocked ligand-mediated receptor signal transduction and cellular proliferation in vitro. They also induced IGF-1R downregulation and catabolism following antibody-mediated endocytosis. These antibodies exhibited activity against human, primate, and rodent IGF-1Rs, and dose-dependently inhibited the growth of established human tumors in nude mice.These fully human antibodies therefore have the potential to provide an effective anti-tumor biological therapy in the human clinical setting. |
| Databáze: | OpenAIRE |
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