Strategies to control therapeutic antibody glycosylation during bioprocessing: Synthesis and separation.
Strategies to control therapeutic antibody glycosylation during bioprocessing: Synthesis and separation.
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DOI：
10.1002/bit.28066
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发表时间：
2022-06
影响因子：
3.8
通讯作者：
Bracewell, Daniel G.
中科院分区：
文献类型：
--
作者：
Edwards, Elizabeth;Livanos, Maria;Krueger, Anja;Dell, Anne;Haslam, Stuart M.;Smales, C. Mark;Bracewell, Daniel G.
糖基化可以是生物制品生产中的关键质量属性。特别是，它对治疗性单克隆抗体（mAb）的半衰期、免疫原性和药代动力学有影响，必须在整个药物开发和生产过程中进行密切监测。为了解决这一问题，主要在上游加工方面取得了进展，包括哺乳动物细胞系工程，以产生更可预测的糖基化mAb，并在发酵期间添加培养基补充剂以操纵糖基化中涉及的代谢途径。一个更强大的方法将是一个联合的上游-下游处理策略。这可能包括实施新的下游技术，例如使用基于Fc γ的亲和配体分离mAb糖变体。本综述强调了控制治疗性抗体糖基化模式的重要性，mAb生物仿制药开发过程中糖基化方面面临的挑战，目前上游和下游控制糖基化的努力及其局限性，以及在下游空间进行研究以建立用于生产抗体疗法的整体和一致的制造工艺的必要性。综述了控制抗体糖基化的上游和下游加工策略。Edwards等人已经提出了上游和下游加工中的各种方法，以将抗体糖基化导向某些谱。上游实例包括细胞系工程、培养基补充和操纵生物反应器条件。下游技术也得到了发展，例如使用Fc γ受体3a亲和配体进行糖变体分离，但作者强调，这一领域的发展明显较少。
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. Upstream and downstream processing strategies to control antibody glycosylation are reviewed. Edwards et al. have presented various approaches in both upstream and downstream processing to direct antibody glycosylation towards certain profiles. Upstream examples include cell line engineering, media supplementation, and manipulating bioreactor conditions. Downstream techniques have also been developed such as the use of Fc γ‐receptor 3a affinity ligands for glycovariant separations, but the authors have highlighted that there is notably less development in this area.
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影响因子：
7.4
作者：
D'Atri, Valentina;Fekete, Szabolcs;Guillarme, Davy
通讯作者：
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影响因子：
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作者：
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DOI：
10.3390/ph3010146
发表时间：
2010-01-12
期刊：
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影响因子：
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通讯作者：
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作者：
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通讯作者：
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