Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies

ABSTRACTMonoclonal antibodies have become an important class of therapeutics in the last 30 years. Because the mechanism of action of therapeutic antibodies is intimately linked to their binding epitopes, identification of the epitope of an antibody to the antigen plays a central role during antibod...

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Main Authors: Xibei Dang (Author), Lars Guelen (Author), David Lutje Hulsik (Author), Grigori Ermakov (Author), Edward J. Hsieh (Author), Joost Kreijtz (Author), Judith Stammen-Vogelzangs (Author), Imke Lodewijks (Author), Astrid Bertens (Author), Arne Bramer (Author), Marco Guadagnoli (Author), Alexis Nazabal (Author), Andrea van Elsas (Author), Thierry Fischmann (Author), Veronica Juan (Author), Amy Beebe (Author), Maribel Beaumont (Author), Hans van Eenennaam (Author)
Format: Book
Published: Taylor & Francis Group, 2023-12-01T00:00:00Z.
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100 1 0 |a Xibei Dang  |e author 
700 1 0 |a Lars Guelen  |e author 
700 1 0 |a David Lutje Hulsik  |e author 
700 1 0 |a Grigori Ermakov  |e author 
700 1 0 |a Edward J. Hsieh  |e author 
700 1 0 |a Joost Kreijtz  |e author 
700 1 0 |a Judith Stammen-Vogelzangs  |e author 
700 1 0 |a Imke Lodewijks  |e author 
700 1 0 |a Astrid Bertens  |e author 
700 1 0 |a Arne Bramer  |e author 
700 1 0 |a Marco Guadagnoli  |e author 
700 1 0 |a Alexis Nazabal  |e author 
700 1 0 |a Andrea van Elsas  |e author 
700 1 0 |a Thierry Fischmann  |e author 
700 1 0 |a Veronica Juan  |e author 
700 1 0 |a Amy Beebe  |e author 
700 1 0 |a Maribel Beaumont  |e author 
700 1 0 |a Hans van Eenennaam  |e author 
245 0 0 |a Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies 
260 |b Taylor & Francis Group,   |c 2023-12-01T00:00:00Z. 
500 |a 10.1080/19420862.2023.2285285 
500 |a 1942-0870 
500 |a 1942-0862 
520 |a ABSTRACTMonoclonal antibodies have become an important class of therapeutics in the last 30 years. Because the mechanism of action of therapeutic antibodies is intimately linked to their binding epitopes, identification of the epitope of an antibody to the antigen plays a central role during antibody drug development. The gold standard of epitope mapping, X-ray crystallography, requires a high degree of proficiency with no guarantee of success. Here, we evaluated six widely used alternative methods for epitope identification (peptide array, alanine scan, domain exchange, hydrogen-deuterium exchange, chemical cross-linking, and hydroxyl radical footprinting) in five antibody-antigen combinations (pembrolizumab+PD1, nivolumab+PD1, ipilimumab+CTLA4, tremelimumab+CTLA4, and MK-5890+CD27). The advantages and disadvantages of each technique are demonstrated by our data and practical advice on when and how to apply specific epitope mapping techniques during the drug development process is provided. Our results suggest chemical cross-linking most accurately identifies the epitope as defined by crystallography. 
546 |a EN 
690 |a Alanine scan 
690 |a cross-linking 
690 |a Epitope mapping 
690 |a Hydrogen deuterium exchange 
690 |a hydroxyl radical footprinting 
690 |a monoclonal antibodies 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
690 |a Immunologic diseases. Allergy 
690 |a RC581-607 
655 7 |a article  |2 local 
786 0 |n mAbs, Vol 15, Iss 1 (2023) 
787 0 |n https://www.tandfonline.com/doi/10.1080/19420862.2023.2285285 
787 0 |n https://doaj.org/toc/1942-0862 
787 0 |n https://doaj.org/toc/1942-0870 
856 4 1 |u https://doaj.org/article/23e30f5d2f8c4516bac906e80f9ad9d7  |z Connect to this object online.