High-mannose glycans on the Fc region of therapeutic IgG antibodies increase serum clearance in humans

作者: A. M. Goetze , Y. D. Liu , Z. Zhang , B. Shah , E. Lee

DOI: 10.1093/GLYCOB/CWR027

关键词: GlycoproteinFragment crystallizable regionAntibodyChemistryImmunoglobulin GMonoclonal antibodyImmunoglobulin Fc FragmentsGlycanBiochemistryMannose

摘要: Glycan structures attached to the CH2 domain of the Fc region of immunoglobulin G (IgG) are essential for specific effector functions but their role in modulating clearance is less clear. Clearance is of obvious importance for therapeutic monoclonal antibodies (Mabs) as it directly impacts efficacy. Here, we study the impact of Fc glycan structure on the clearance of four therapeutic human IgGs (one IgG1 and three IgG2s) in humans. The therapeutic IgGs were affinity purified from serum samples from human pharmacokinetic studies, and …

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