Bivalent non-human gal-α1-3-gal glycan epitopes in the Fc region of a monoclonal antibody model can be recognized by anti-Gal-α1-3-Gal IgE antibodies
ABSTRACTMonoclonal antibody (mAb) production using non-human cells can introduce non-human glycan epitopes including terminal galactosyl-α1–3-galactose (α1–3-Gal) moieties. Cetuximab is a commercial mAb associated with causing anaphylaxis in some patients due to the binding of endogenous anti-α1–3-G...
| 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/10.1080/19420862.2023.2239405 |
| _version_ | 1827240475451457536 |
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| author | Grayson Hatfield Lioudmila Tepliakova Jessica Tran Huixin Lu Michel Gilbert Roger Y. Tam |
| author_facet | Grayson Hatfield Lioudmila Tepliakova Jessica Tran Huixin Lu Michel Gilbert Roger Y. Tam |
| author_sort | Grayson Hatfield |
| collection | DOAJ |
| description | ABSTRACTMonoclonal antibody (mAb) production using non-human cells can introduce non-human glycan epitopes including terminal galactosyl-α1–3-galactose (α1–3-Gal) moieties. Cetuximab is a commercial mAb associated with causing anaphylaxis in some patients due to the binding of endogenous anti-α1–3-Gal IgE to the Fab (containing bi-α1–3-galactosylated glycans) but not to the Fc region (containing mono-α1–3-galactosylated glycans). Despite being low in abundance in typical commercial mAbs, the inherent sensitivity of cell culture conditions on glycosylation profiles, and the development of novel glycoengineering strategies, novel antibody-based modalities, and biosimilars by various manufacturers with varying procedures, necessitates a better understanding of the structural requirements for anti-α1–3-Gal IgE binding to the Fc region. Herein, we synthesized mAb glycoforms with varying degrees and regioisomers of α1–3-galactosylation and tested their binding to two commercial anti-α1–3-Gal human IgE antibodies derived from a human patient with allergies to red meat (comprising α1–3-Gal epitopes), as well as to the FcγRIIIA receptor. Our results demonstrate that unexpectedly, anti-α1–3-Gal human IgE antibodies can bind to Fc glycans, with bi-α1–3-galactosylation being the most important factor, highlighting that their presence in the Fc region may be considered as a potential critical quality attribute, particularly when using novel platforms in mAb-based biotherapeutics. |
| first_indexed | 2024-03-08T14:24:12Z |
| format | Article |
| id | doaj.art-6d92f17abccf4bbdafad13f1e090a7ab |
| institution | Directory Open Access Journal |
| issn | 1942-0862 1942-0870 |
| language | English |
| last_indexed | 2025-03-21T21:25:11Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj.art-6d92f17abccf4bbdafad13f1e090a7ab2024-05-28T15:55:46ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2023.2239405Bivalent non-human gal-α1-3-gal glycan epitopes in the Fc region of a monoclonal antibody model can be recognized by anti-Gal-α1-3-Gal IgE antibodiesGrayson Hatfield0Lioudmila Tepliakova1Jessica Tran2Huixin Lu3Michel Gilbert4Roger Y. Tam5Centre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Canada, Ottawa, Ontario, CanadaCentre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Canada, Ottawa, Ontario, CanadaCentre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Canada, Ottawa, Ontario, CanadaCentre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Canada, Ottawa, Ontario, CanadaHuman Health Therapeutics Research Centre, National Research Council Canada, Ottawa, Ontario, CanadaCentre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Canada, Ottawa, Ontario, CanadaABSTRACTMonoclonal antibody (mAb) production using non-human cells can introduce non-human glycan epitopes including terminal galactosyl-α1–3-galactose (α1–3-Gal) moieties. Cetuximab is a commercial mAb associated with causing anaphylaxis in some patients due to the binding of endogenous anti-α1–3-Gal IgE to the Fab (containing bi-α1–3-galactosylated glycans) but not to the Fc region (containing mono-α1–3-galactosylated glycans). Despite being low in abundance in typical commercial mAbs, the inherent sensitivity of cell culture conditions on glycosylation profiles, and the development of novel glycoengineering strategies, novel antibody-based modalities, and biosimilars by various manufacturers with varying procedures, necessitates a better understanding of the structural requirements for anti-α1–3-Gal IgE binding to the Fc region. Herein, we synthesized mAb glycoforms with varying degrees and regioisomers of α1–3-galactosylation and tested their binding to two commercial anti-α1–3-Gal human IgE antibodies derived from a human patient with allergies to red meat (comprising α1–3-Gal epitopes), as well as to the FcγRIIIA receptor. Our results demonstrate that unexpectedly, anti-α1–3-Gal human IgE antibodies can bind to Fc glycans, with bi-α1–3-galactosylation being the most important factor, highlighting that their presence in the Fc region may be considered as a potential critical quality attribute, particularly when using novel platforms in mAb-based biotherapeutics.https://www.tandfonline.com/doi/10.1080/19420862.2023.2239405GlycosylationIgEmonoclonal antibodiesnon-human glycans |
| spellingShingle | Grayson Hatfield Lioudmila Tepliakova Jessica Tran Huixin Lu Michel Gilbert Roger Y. Tam Bivalent non-human gal-α1-3-gal glycan epitopes in the Fc region of a monoclonal antibody model can be recognized by anti-Gal-α1-3-Gal IgE antibodies mAbs Glycosylation IgE monoclonal antibodies non-human glycans |
| title | Bivalent non-human gal-α1-3-gal glycan epitopes in the Fc region of a monoclonal antibody model can be recognized by anti-Gal-α1-3-Gal IgE antibodies |
| title_full | Bivalent non-human gal-α1-3-gal glycan epitopes in the Fc region of a monoclonal antibody model can be recognized by anti-Gal-α1-3-Gal IgE antibodies |
| title_fullStr | Bivalent non-human gal-α1-3-gal glycan epitopes in the Fc region of a monoclonal antibody model can be recognized by anti-Gal-α1-3-Gal IgE antibodies |
| title_full_unstemmed | Bivalent non-human gal-α1-3-gal glycan epitopes in the Fc region of a monoclonal antibody model can be recognized by anti-Gal-α1-3-Gal IgE antibodies |
| title_short | Bivalent non-human gal-α1-3-gal glycan epitopes in the Fc region of a monoclonal antibody model can be recognized by anti-Gal-α1-3-Gal IgE antibodies |
| title_sort | bivalent non human gal α1 3 gal glycan epitopes in the fc region of a monoclonal antibody model can be recognized by anti gal α1 3 gal ige antibodies |
| topic | Glycosylation IgE monoclonal antibodies non-human glycans |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2023.2239405 |
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