Systematic analysis of Fc mutations designed to enhance binding to Fc-gamma receptors
A critical attribute of therapeutic antibodies is their ability to engage with humoral or cellular effector mechanisms, and this depends on the ability of the Fc region to bind to complement (C1q) or Fc receptors. Investigators have sought to optimize these effects by engineering the Fc region to bi...
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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/10.1080/19420862.2024.2406539 |
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| _version_ | 1832576543526748160 |
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| author | Geoff Hale Alastair Douglas Davy Ian Wilkinson |
| author_facet | Geoff Hale Alastair Douglas Davy Ian Wilkinson |
| author_sort | Geoff Hale |
| collection | DOAJ |
| description | A critical attribute of therapeutic antibodies is their ability to engage with humoral or cellular effector mechanisms, and this depends on the ability of the Fc region to bind to complement (C1q) or Fc receptors. Investigators have sought to optimize these effects by engineering the Fc region to bind to a greater or lesser extent to individual receptors. 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 representing a range of variants and compared their activity in cell-based assays for complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent phagocytosis using a range of individual Fc receptors. We have also compared the thermal stability of the variants by differential scanning fluorimetry (DSF). The results reveal a spectrum of activities which may be appropriate for different applications. |
| format | Article |
| id | doaj-art-510b104248724183bfa4bd7e26ced614 |
| 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-510b104248724183bfa4bd7e26ced6142025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2406539Systematic analysis of Fc mutations designed to enhance binding to Fc-gamma receptorsGeoff Hale0Alastair Douglas Davy1Ian Wilkinson2mAbsolve Limited, Oxford, UKProtein Stable Ltd, Leatherhead, UKmAbsolve Limited, Oxford, UKA critical attribute of therapeutic antibodies is their ability to engage with humoral or cellular effector mechanisms, and this depends on the ability of the Fc region to bind to complement (C1q) or Fc receptors. Investigators have sought to optimize these effects by engineering the Fc region to bind to a greater or lesser extent to individual receptors. 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 representing a range of variants and compared their activity in cell-based assays for complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent phagocytosis using a range of individual Fc receptors. We have also compared the thermal stability of the variants by differential scanning fluorimetry (DSF). The results reveal a spectrum of activities which may be appropriate for different applications.https://www.tandfonline.com/doi/10.1080/19420862.2024.2406539DSFFc regionFc receptortherapeutic antibodyantibody engineeringFcγRI |
| spellingShingle | Geoff Hale Alastair Douglas Davy Ian Wilkinson Systematic analysis of Fc mutations designed to enhance binding to Fc-gamma receptors mAbs DSF Fc region Fc receptor therapeutic antibody antibody engineering FcγRI |
| title | Systematic analysis of Fc mutations designed to enhance binding to Fc-gamma receptors |
| title_full | Systematic analysis of Fc mutations designed to enhance binding to Fc-gamma receptors |
| title_fullStr | Systematic analysis of Fc mutations designed to enhance binding to Fc-gamma receptors |
| title_full_unstemmed | Systematic analysis of Fc mutations designed to enhance binding to Fc-gamma receptors |
| title_short | Systematic analysis of Fc mutations designed to enhance binding to Fc-gamma receptors |
| title_sort | systematic analysis of fc mutations designed to enhance binding to fc gamma receptors |
| topic | DSF Fc region Fc receptor therapeutic antibody antibody engineering FcγRI |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2406539 |
| work_keys_str_mv | AT geoffhale systematicanalysisoffcmutationsdesignedtoenhancebindingtofcgammareceptors AT alastairdouglasdavy systematicanalysisoffcmutationsdesignedtoenhancebindingtofcgammareceptors AT ianwilkinson systematicanalysisoffcmutationsdesignedtoenhancebindingtofcgammareceptors |