Glyco-engineering of Fc Glycans to Enhance the Biological Functions of Therapeutic IgGs

  • T. Shantha RajuEmail author
  • David M. Knight
  • Robert E. Jordan


Glycans N-linked to the Fc region of IgGs affect binding to various Fc receptors and C1q protein and therefore are important for IgG effector functions, including ADCC and CDC activities. Fc glycans are highly heterogeneous and the nature of this variation differs between species. Heterogeneity of Fc glycans arises from the presence or the absence of different terminal sugars, including sialic acid, galactose and N-acetylglucosamine, core fucose along with bisecting N-acetylglucosamine. To understand the influence of individual terminal sugar residues on serum half-life and antibody effector functions, it is necessary to prepare homogeneous IgG glycoforms. This chapter describes glycoengineering strategies to prepare IgG molecules containing homogeneous glycan chains in the Fc region and their significance in assessing IgG functions. The importance of selecting appropriate in vitro and/or in vivo conditions, including enzymes, buffers and cell culture conditions, to produce recombinant IgGs with homogeneous glycoforms is discussed.


Immunoglobulins Antibody Glycosylation Glycans Glycoengineering Recombinant IgG 



antibody dependent cellular cytotoxicity


complement dependent cytotoxicity


capillary electrophoresis with laser induced fluorescence detection


Chinese hamster ovary


cytidine monophosphate N-acetylneuraminic acid


2,5-Dihydroxybenzoic acid




electrospray ionization mass spectrometry










ion exchange chromatography


immunoglobulin G


matrix-assisted laser/desorption ionization time-of-flight mass spectrometry



PNGase F

peptide N-glycosidase F


recombinant immunoglobulin G


reversed phase high-performance liquid chromatography


sialic acid (N-acetylneuraminic acid)


tissue plasminogen activator


uridine diphosphate galactose


uridine diphosphate N-acetylglucosamine










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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • T. Shantha Raju
    • 1
    Email author
  • David M. Knight
    • 1
  • Robert E. Jordan
    • 1
  1. 1.Discovery Technology ResearchBiologics Research, Centocor R&D IncRadnorUSA

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