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Strategies to control therapeutic antibody glycosylation during bioprocessing: Synthesis and separation

Glycosylation can be a critical quality attribute in biologic manufacturing. In particular, it has implications on the half‐life, immunogenicity, and pharmacokinetics of therapeutic monoclonal antibodies (mAbs), and must be closely monitored throughout drug development and manufacturing. To address...

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Autores principales: Edwards, Elizabeth, Livanos, Maria, Krueger, Anja, Dell, Anne, Haslam, Stuart M., Mark Smales, C., Bracewell, Daniel G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310845/
https://www.ncbi.nlm.nih.gov/pubmed/35182428
http://dx.doi.org/10.1002/bit.28066
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author Edwards, Elizabeth
Livanos, Maria
Krueger, Anja
Dell, Anne
Haslam, Stuart M.
Mark Smales, C.
Bracewell, Daniel G.
author_facet Edwards, Elizabeth
Livanos, Maria
Krueger, Anja
Dell, Anne
Haslam, Stuart M.
Mark Smales, C.
Bracewell, Daniel G.
author_sort Edwards, Elizabeth
collection PubMed
description Glycosylation can be a critical quality attribute in biologic manufacturing. In particular, it has implications on the half‐life, immunogenicity, and pharmacokinetics of therapeutic monoclonal antibodies (mAbs), and must be closely monitored throughout drug development and manufacturing. To address this, advances have been made primarily in upstream processing, including mammalian cell line engineering, to yield more predictably glycosylated mAbs and the addition of media supplements during fermentation to manipulate the metabolic pathways involved in glycosylation. A more robust approach would be a conjoined upstream–downstream processing strategy. This could include implementing novel downstream technologies, such as the use of Fc γ‐based affinity ligands for the separation of mAb glycovariants. This review highlights the importance of controlling therapeutic antibody glycosylation patterns, the challenges faced in terms of glycosylation during mAb biosimilar development, current efforts both upstream and downstream to control glycosylation and their limitations, and the need for research in the downstream space to establish holistic and consistent manufacturing processes for the production of antibody therapies.
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spelling pubmed-93108452022-07-29 Strategies to control therapeutic antibody glycosylation during bioprocessing: Synthesis and separation Edwards, Elizabeth Livanos, Maria Krueger, Anja Dell, Anne Haslam, Stuart M. Mark Smales, C. Bracewell, Daniel G. Biotechnol Bioeng REVIEWS Glycosylation can be a critical quality attribute in biologic manufacturing. In particular, it has implications on the half‐life, immunogenicity, and pharmacokinetics of therapeutic monoclonal antibodies (mAbs), and must be closely monitored throughout drug development and manufacturing. To address this, advances have been made primarily in upstream processing, including mammalian cell line engineering, to yield more predictably glycosylated mAbs and the addition of media supplements during fermentation to manipulate the metabolic pathways involved in glycosylation. A more robust approach would be a conjoined upstream–downstream processing strategy. This could include implementing novel downstream technologies, such as the use of Fc γ‐based affinity ligands for the separation of mAb glycovariants. This review highlights the importance of controlling therapeutic antibody glycosylation patterns, the challenges faced in terms of glycosylation during mAb biosimilar development, current efforts both upstream and downstream to control glycosylation and their limitations, and the need for research in the downstream space to establish holistic and consistent manufacturing processes for the production of antibody therapies. John Wiley and Sons Inc. 2022-02-28 2022-06 /pmc/articles/PMC9310845/ /pubmed/35182428 http://dx.doi.org/10.1002/bit.28066 Text en © 2022 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle REVIEWS
Edwards, Elizabeth
Livanos, Maria
Krueger, Anja
Dell, Anne
Haslam, Stuart M.
Mark Smales, C.
Bracewell, Daniel G.
Strategies to control therapeutic antibody glycosylation during bioprocessing: Synthesis and separation
title Strategies to control therapeutic antibody glycosylation during bioprocessing: Synthesis and separation
title_full Strategies to control therapeutic antibody glycosylation during bioprocessing: Synthesis and separation
title_fullStr Strategies to control therapeutic antibody glycosylation during bioprocessing: Synthesis and separation
title_full_unstemmed Strategies to control therapeutic antibody glycosylation during bioprocessing: Synthesis and separation
title_short Strategies to control therapeutic antibody glycosylation during bioprocessing: Synthesis and separation
title_sort strategies to control therapeutic antibody glycosylation during bioprocessing: synthesis and separation
topic REVIEWS
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310845/
https://www.ncbi.nlm.nih.gov/pubmed/35182428
http://dx.doi.org/10.1002/bit.28066
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