Fc glycan sialylation of biotherapeutic monoclonal antibodies has limited impact on antibody‐dependent cellular cytotoxicity
It has been well documented that the terminal sugars of Fc glycans can play a critical role in the safety and efficacy of therapeutic mAbs. However, many of the effects of highly heterogeneous Fc glycan structures have yet to be fully characterized. Different glycosylation patterns can affect Fc‐dep...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-11-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13267 |
| _version_ | 1819260019098517504 |
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| author | Elaine Branstetter Robert J. Duff Scott Kuhns Rupa Padaki |
| author_facet | Elaine Branstetter Robert J. Duff Scott Kuhns Rupa Padaki |
| author_sort | Elaine Branstetter |
| collection | DOAJ |
| description | It has been well documented that the terminal sugars of Fc glycans can play a critical role in the safety and efficacy of therapeutic mAbs. However, many of the effects of highly heterogeneous Fc glycan structures have yet to be fully characterized. Different glycosylation patterns can affect Fc‐dependent activities, such as the ability of mAbs to bind Fcγ receptors on the effector cell surface, which is critical to immune effector functions, such as antibody‐dependent cellular cytotoxicity (ADCC). Previous studies on the impact of sialic acid in the Fc glycan on ADCC have not resulted in consistent conclusions. In our study, we tested sialic acid‐enriched species from a chimeric murine/human kappa light chain IgG1 (mAb1) with known Fcγ receptor IIIa binding and ADCC activities. These enriched species contained up to a fourfold increase in sialic acid‐containing glycans relative to the typical levels present in therapeutic mAbs, along with other attributes such as oxidized and deamidated species. The ADCC analysis of sialylated and asialo mAb1 provided herein shows evidence that sialic acids have little or no impact on ADCC activity. Altogether, our results highlight the value of novel glycan engineering strategies in designing therapeutic mAbs with high‐quality attributes and in improving production process controls. |
| first_indexed | 2024-12-23T19:19:15Z |
| format | Article |
| id | doaj.art-f08697e91998419f8ca34d8371196493 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-12-23T19:19:15Z |
| publishDate | 2021-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-f08697e91998419f8ca34d83711964932022-12-21T17:34:13ZengWileyFEBS Open Bio2211-54632021-11-0111112943294910.1002/2211-5463.13267Fc glycan sialylation of biotherapeutic monoclonal antibodies has limited impact on antibody‐dependent cellular cytotoxicityElaine Branstetter0Robert J. Duff1Scott Kuhns2Rupa Padaki3Department of Attribute Sciences Amgen Inc. Thousand Oaks CA USADepartment of Attribute Sciences Amgen Inc. Thousand Oaks CA USADepartment of Attribute Sciences Amgen Inc. Thousand Oaks CA USADepartment of Attribute Sciences Amgen Inc. Thousand Oaks CA USAIt has been well documented that the terminal sugars of Fc glycans can play a critical role in the safety and efficacy of therapeutic mAbs. However, many of the effects of highly heterogeneous Fc glycan structures have yet to be fully characterized. Different glycosylation patterns can affect Fc‐dependent activities, such as the ability of mAbs to bind Fcγ receptors on the effector cell surface, which is critical to immune effector functions, such as antibody‐dependent cellular cytotoxicity (ADCC). Previous studies on the impact of sialic acid in the Fc glycan on ADCC have not resulted in consistent conclusions. In our study, we tested sialic acid‐enriched species from a chimeric murine/human kappa light chain IgG1 (mAb1) with known Fcγ receptor IIIa binding and ADCC activities. These enriched species contained up to a fourfold increase in sialic acid‐containing glycans relative to the typical levels present in therapeutic mAbs, along with other attributes such as oxidized and deamidated species. The ADCC analysis of sialylated and asialo mAb1 provided herein shows evidence that sialic acids have little or no impact on ADCC activity. Altogether, our results highlight the value of novel glycan engineering strategies in designing therapeutic mAbs with high‐quality attributes and in improving production process controls.https://doi.org/10.1002/2211-5463.13267glycan profilingantibody‐dependent cellular cytotoxicitysialylationIgG glycosylationmonoclonal antibodymAb |
| spellingShingle | Elaine Branstetter Robert J. Duff Scott Kuhns Rupa Padaki Fc glycan sialylation of biotherapeutic monoclonal antibodies has limited impact on antibody‐dependent cellular cytotoxicity FEBS Open Bio glycan profiling antibody‐dependent cellular cytotoxicity sialylation IgG glycosylation monoclonal antibody mAb |
| title | Fc glycan sialylation of biotherapeutic monoclonal antibodies has limited impact on antibody‐dependent cellular cytotoxicity |
| title_full | Fc glycan sialylation of biotherapeutic monoclonal antibodies has limited impact on antibody‐dependent cellular cytotoxicity |
| title_fullStr | Fc glycan sialylation of biotherapeutic monoclonal antibodies has limited impact on antibody‐dependent cellular cytotoxicity |
| title_full_unstemmed | Fc glycan sialylation of biotherapeutic monoclonal antibodies has limited impact on antibody‐dependent cellular cytotoxicity |
| title_short | Fc glycan sialylation of biotherapeutic monoclonal antibodies has limited impact on antibody‐dependent cellular cytotoxicity |
| title_sort | fc glycan sialylation of biotherapeutic monoclonal antibodies has limited impact on antibody dependent cellular cytotoxicity |
| topic | glycan profiling antibody‐dependent cellular cytotoxicity sialylation IgG glycosylation monoclonal antibody mAb |
| url | https://doi.org/10.1002/2211-5463.13267 |
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