Isolation of scFvs toIn VitroProduced Extracellular Domains of EGFR Family Members
| Autor: | James D. Marks, Maria Russeva, Yu Zhou, Jennifer L. Garrison, Polina Furmanova, Qing-An Yuan, Gregory P. Adams, Louis M. Weiner, Heidi H. Simmons, Tara Heitner, Jianlong Lou, Matthew K. Robinson, Eva M. Horak |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Receptor ErbB-4 Phage display medicine.drug_class Molecular Sequence Data Immunoglobulin Variable Region Kidney Transfection Monoclonal antibody Cell Line Cell Line Tumor medicine Humans Radiology Nuclear Medicine and imaging Epidermal growth factor receptor Cloning Molecular Gene DNA Primers Ovarian Neoplasms Pharmacology Base Sequence biology HEK 293 cells General Medicine Molecular biology In vitro ErbB Receptors Oncology biology.protein Female Antibody |
| Zdroj: | Cancer Biotherapy and Radiopharmaceuticals. 20:603-613 |
| ISSN: | 1557-8852 1084-9785 |
| DOI: | 10.1089/cbr.2005.20.603 |
| Popis: | The members of the epidermal growth factor receptor (EGFR) family are over expressed in a variety of malignancies and are frequently linked to aggressive disease and a poor prognosis. Although clinically effective monoclonal antibodies (MAbs) have been developed to target HER2 and EGFR, the remaining two family members, HER3 and HER4, have not been the subject of significant efforts. In this paper, we have taken the initial steps required to generate antibodies with potential clinically utility that target the members of the EGFR family. The genes for the extracellular domains (ECDs) of all four members of the EGFR family were cloned and used to stably transfect 293 (HEK) cells. Milligram quantities of each ECD were produced and characterized. The HER3, HER4, and EGFR ECDs were then employed as targets for the selection of antibodies from naïve human scFv (single-chain Fv) phage display libraries. Six unique scFv clones were isolated that bound specifically to HER3, 13 unique clones were isolated with specificity for HER4 and 52 unique anti-EGFR clones were isolated. These scFvs provide a valuable and potentially clinically relevant panel of agents to target the members of the EGFR family. |
| Databáze: | OpenAIRE |
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