Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors
Elimination of the binding of immunoglobulin Fc to Fc gamma receptors is highly desirable for the avoidance of unwanted inflammatory responses to therapeutic antibodies and fusion proteins. Many different approaches have been used in the clinic, but they have not been systematically compared. We hav...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2402701 |
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| _version_ | 1832576547963273216 |
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| author | Geoff Hale Jelle De Vos Alastair Douglas Davy Koen Sandra Ian Wilkinson |
| author_facet | Geoff Hale Jelle De Vos Alastair Douglas Davy Koen Sandra Ian Wilkinson |
| author_sort | Geoff Hale |
| collection | DOAJ |
| description | Elimination of the binding of immunoglobulin Fc to Fc gamma receptors is highly desirable for the avoidance of unwanted inflammatory responses to therapeutic antibodies and fusion proteins. Many different approaches have been used in the clinic, but they have not been systematically compared. We have now produced a matched set of anti-CD20 antibodies with different Fc subclasses and variants and compared their activity for binding to C1q, Fc-gamma receptors and in cell-based assays. Most of the variants still have significant levels of activity in one or more of these assays and many of them have impaired temperature stability compared with the corresponding wild-type antibody. |
| format | Article |
| id | doaj-art-62ff2163c22f4831b54f543b2073ecdf |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-62ff2163c22f4831b54f543b2073ecdf2025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2402701Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptorsGeoff Hale0Jelle De Vos1Alastair Douglas Davy2Koen Sandra3Ian Wilkinson4mAbsolve Limited, Oxford, UKRIC group, Kortrijk, BelgiumProtein Stable Ltd, Leatherhead, UKRIC group, Kortrijk, BelgiummAbsolve Limited, Oxford, UKElimination of the binding of immunoglobulin Fc to Fc gamma receptors is highly desirable for the avoidance of unwanted inflammatory responses to therapeutic antibodies and fusion proteins. Many different approaches have been used in the clinic, but they have not been systematically compared. We have now produced a matched set of anti-CD20 antibodies with different Fc subclasses and variants and compared their activity for binding to C1q, Fc-gamma receptors and in cell-based assays. Most of the variants still have significant levels of activity in one or more of these assays and many of them have impaired temperature stability compared with the corresponding wild-type antibody.https://www.tandfonline.com/doi/10.1080/19420862.2024.2402701DSFFc regionFc receptorFc silenttherapeutic antibodyantibody engineering |
| spellingShingle | Geoff Hale Jelle De Vos Alastair Douglas Davy Koen Sandra Ian Wilkinson Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors mAbs DSF Fc region Fc receptor Fc silent therapeutic antibody antibody engineering |
| title | Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors |
| title_full | Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors |
| title_fullStr | Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors |
| title_full_unstemmed | Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors |
| title_short | Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors |
| title_sort | systematic analysis of fc mutations designed to reduce binding to fc gamma receptors |
| topic | DSF Fc region Fc receptor Fc silent therapeutic antibody antibody engineering |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2402701 |
| work_keys_str_mv | AT geoffhale systematicanalysisoffcmutationsdesignedtoreducebindingtofcgammareceptors AT jelledevos systematicanalysisoffcmutationsdesignedtoreducebindingtofcgammareceptors AT alastairdouglasdavy systematicanalysisoffcmutationsdesignedtoreducebindingtofcgammareceptors AT koensandra systematicanalysisoffcmutationsdesignedtoreducebindingtofcgammareceptors AT ianwilkinson systematicanalysisoffcmutationsdesignedtoreducebindingtofcgammareceptors |