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Delineating the functional map of the interaction between nimotuzumab and the epidermal growth factor receptor
- Source :
- mAbs. 6(4)
- Publication Year :
- 2014
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 19420870
- Volume :
- 6
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- mAbs
- Accession number :
- edsair.doi.dedup.....2730aca4bc67a5cb1e06340665b421b3