Delineating the functional map of the interaction between nimotuzumab and the epidermal growth factor receptor
| Autor: | Amaury Pupo, Claudia Patricia García-Hernández, Yaima Tundidor, Gertrudis Rojas, Yanelys Cabrera Infante |
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| Rok vydání: | 2014 |
| Předmět: |
Phage display
biology In silico Immunology Computational biology Antibodies Monoclonal Humanized Molecular biology Epitope Protein Structure Tertiary ErbB Receptors Epitopes Epitope mapping Antibody Specificity Report biology.protein medicine Immunology and Allergy Nimotuzumab Humans Paratope Epidermal growth factor receptor Binding site Epitope Mapping medicine.drug |
| Zdroj: | mAbs. 6(4) |
| ISSN: | 1942-0870 |
| Popis: | Molecular details of epidermal growth factor receptor (EGFR) targeting by nimotuzumab, a therapeutic anti-cancer antibody, have been largely unknown. The current study delineated a functional map of their interface, based on phage display and extensive mutagenesis of both the target antigen and the Fv antibody fragment. Five residues in EGFR domain III (R353, S356, F357, T358, and H359T) and the third hypervariable region of nimotuzumab heavy chain were shown to be major functional contributors to the interaction. Fine specificity differences between nimotuzumab and other anti-EGFR antibodies were revealed. Mapping information guided the generation of a plausible in silico binding model. Knowledge about the epitope/paratope interface opens new avenues for the study of tumor sensitivity/resistance to nimotuzumab and for further engineering of its binding site. The developed mapping platform, also validated with the well-known cetuximab epitope, allows a comprehensive exploration of antigenic regions and could be expanded to map other anti-EGFR antibodies. |
| Databáze: | OpenAIRE |
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