Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: the high-mannose, hybrid, and complex types Jordi Pelkmans Amanda Maurits

Antigen-IgG1-FcγRIIIa binding Antibody Dependent Cellular Cytotoxicity (ADCC) FcγRIIIa

C1q Antigen-IgG1-C1q binding Complement Dependent Cytotoxicity (CDC)

Human IgG1

Three types of N-linked oligosaccharides High-mannose Hybrid Complex All types can be fucosylated

Different types of oligosaccharides created in this article No difference in binding of the variable part of the IgG1 was observed

Difference in binding affinity to FcγRIIIa

Difference in ADCC activity

Contamination of different types of oligosaccharides influences activity of Fu(-) Complex type

Difference in CDC activity

C1q binds best to Complex type

Plasma clearance of different types

The FcRn receptor Binds IgG1 and prevents its degradation

Conclusion Oligosac charide FcγRIIIa binding affinity ADCC activity CDC activity C1q binding affinity Plasma clearance in mice FcRn binding affinity Fu(-) Complex Fu(+) Complex Fu(-) Hybrid Fu(+) Hybrid Fu(-) M8, Fu(-) M

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