N-glycosylation heterogeneity and the influence on structure, function and pharmacokinetics of monoclonal antibodies and Fc fusion proteins

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• 作者：Fabian Higel^a ; ^{fabian.higel@sandoz.com" class="auth_mail" title="E-mail the corresponding author} ; Andreas Seidl^a ; Fritz Sö ; rgel^b ; ^c ; Wolfgang Friess^d
• 关键词：Monoclonal antibody ; Fusion protein ; N-glycosylation ; Pharmacokinetics ; Glyco-engineering
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：100
• 期：Complete
• 页码：94-100
• 全文大小：691 K

文摘

Monoclonal antibody and Fc fusion protein drugs are complex heterogeneous mixtures of numerous different protein variants and modifications. N-glycosylation as one of the most complex post-translational modification influences the structural characteristics of the antibodies Fc part thereby potentially modulating effector function and pharmacokinetics. Several investigations on the relationship between N-glycosylation and pharmacokinetics have been published. However, this structure–function relationship is not fully understood. In this review potential alterations with focus on N-glycosylation of mAbs and Fc fusion proteins and the possible effects on the pharmacokinetics are reviewed and the current understandings of the underlying mechanisms are described.