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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2023.2285285 |
| _version_ | 1827240462256177152 |
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| author | Xibei Dang Lars Guelen David Lutje Hulsik Grigori Ermakov Edward J. Hsieh Joost Kreijtz Judith Stammen-Vogelzangs Imke Lodewijks Astrid Bertens Arne Bramer Marco Guadagnoli Alexis Nazabal Andrea van Elsas Thierry Fischmann Veronica Juan Amy Beebe Maribel Beaumont Hans van Eenennaam |
| author_facet | Xibei Dang Lars Guelen David Lutje Hulsik Grigori Ermakov Edward J. Hsieh Joost Kreijtz Judith Stammen-Vogelzangs Imke Lodewijks Astrid Bertens Arne Bramer Marco Guadagnoli Alexis Nazabal Andrea van Elsas Thierry Fischmann Veronica Juan Amy Beebe Maribel Beaumont Hans van Eenennaam |
| author_sort | Xibei Dang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T14:23:56Z |
| format | Article |
| id | doaj.art-23e30f5d2f8c4516bac906e80f9ad9d7 |
| institution | Directory Open Access Journal |
| issn | 1942-0862 1942-0870 |
| language | English |
| last_indexed | 2025-03-21T21:24:58Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj.art-23e30f5d2f8c4516bac906e80f9ad9d72024-05-28T15:55:47ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2023.2285285Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologiesXibei Dang0Lars Guelen1David Lutje Hulsik2Grigori Ermakov3Edward J. Hsieh4Joost Kreijtz5Judith Stammen-Vogelzangs6Imke Lodewijks7Astrid Bertens8Arne Bramer9Marco Guadagnoli10Alexis Nazabal11Andrea van Elsas12Thierry Fischmann13Veronica Juan14Amy Beebe15Maribel Beaumont16Hans van Eenennaam17Pharmacokinetics, Merck & Co. Inc, Kenilworth, NJ, USAResearch, Aduro Biotech Europe, Oss, The NetherlandsResearch, Aduro Biotech Europe, Oss, The NetherlandsPharmacokinetics, Merck & Co. Inc, Kenilworth, NJ, USAPharmacokinetics, Merck & Co. Inc, Kenilworth, NJ, USAResearch, Aduro Biotech Europe, Oss, The NetherlandsResearch, Aduro Biotech Europe, Oss, The NetherlandsResearch, Aduro Biotech Europe, Oss, The NetherlandsResearch, Aduro Biotech Europe, Oss, The NetherlandsResearch, Aduro Biotech Europe, Oss, The NetherlandsResearch, Aduro Biotech Europe, Oss, The NetherlandsMedical, CovalX AG, Zürich, SwitzerlandResearch, Aduro Biotech Europe, Oss, The NetherlandsPharmacokinetics, Merck & Co. Inc, Kenilworth, NJ, USAPharmacokinetics, Merck & Co. Inc, Kenilworth, NJ, USAPharmacokinetics, Merck & Co. Inc, Kenilworth, NJ, USAPharmacokinetics, Merck & Co. Inc, Kenilworth, NJ, USAResearch, Aduro Biotech Europe, Oss, The NetherlandsABSTRACTMonoclonal 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.https://www.tandfonline.com/doi/10.1080/19420862.2023.2285285Alanine scancross-linkingEpitope mappingHydrogen deuterium exchangehydroxyl radical footprintingmonoclonal antibodies |
| spellingShingle | Xibei Dang Lars Guelen David Lutje Hulsik Grigori Ermakov Edward J. Hsieh Joost Kreijtz Judith Stammen-Vogelzangs Imke Lodewijks Astrid Bertens Arne Bramer Marco Guadagnoli Alexis Nazabal Andrea van Elsas Thierry Fischmann Veronica Juan Amy Beebe Maribel Beaumont Hans van Eenennaam Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies mAbs Alanine scan cross-linking Epitope mapping Hydrogen deuterium exchange hydroxyl radical footprinting monoclonal antibodies |
| title | Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies |
| title_full | Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies |
| title_fullStr | Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies |
| title_full_unstemmed | Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies |
| title_short | Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies |
| title_sort | epitope mapping of monoclonal antibodies a comprehensive comparison of different technologies |
| topic | Alanine scan cross-linking Epitope mapping Hydrogen deuterium exchange hydroxyl radical footprinting monoclonal antibodies |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2023.2285285 |
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