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Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: the high-mannose,

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Presentation on theme: "Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: the high-mannose,"— Presentation transcript:

1 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

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

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

4 Human IgG1

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

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

7 Difference in binding affinity to FcγRIIIa

8

9 Difference in ADCC activity

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

11 Difference in CDC activity

12 C1q binds best to Complex type

13 Plasma clearance of different types

14 The FcRn receptor Binds IgG1 and prevents its degradation

15 Conclusion Oligosac charide FcγRIIIa binding affinity ADCC activity CDC activity C1q binding affinity Plasma clearance in mice FcRn binding affinity Fu(-) Complex 666663 Fu(+) Complex 226661 Fu(-) Hybrid 455555 Fu(+) Hybrid 1155-2 Fu(-) M8,9 5455-6 Fu(-) M5335544

16 Questions?


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