Preparation and biological activities of anti-HER2 monoclonal antibodies with fully core-fucosylated homogeneous bi-antennary complex-type glycans

Bioscience, Biotechnology, and Biochemistry
Wataru TsukimuraTakashi Shirai

Abstract

Recently, the absence of a core-fucose residue in the N-glycan has been implicated to be important for enhancing antibody-dependent cellular cytotoxicity (ADCC) activity of immunoglobulin G monoclonal antibodies (mAbs). Here, we first prepared anti-HER2 mAbs having two core-fucosylated N-glycan chains with the single G2F, G1aF, G1bF, or G0F structure, together with those having two N-glycan chains with a single non-core-fucosylated corresponding structure for comparison, and determined their biological activities. Dissociation constants of mAbs with core-fucosylated N-glycans bound to recombinant Fcγ-receptor type IIIa variant were 10 times higher than those with the non-core-fucosylated N-glycans, regardless of core glycan structures. mAbs with the core-fucosylated N-glycans had markedly reduced ADCC activities, while those with the non-core-fucosylated N-glycans had high activities. These results indicate that the presence of a core-fucose residue in the N-glycan suppresses the binding to the Fc-receptor and the induction of ADCC of anti-HER2 mAbs.

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Citations

Apr 23, 2021·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Shino Manabe, Yoshiki Yamaguchi
Jul 3, 2021·International Journal of Molecular Sciences·Catherine Forest-NaultGregory De Crescenzo

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Methods Mentioned

BETA
surface plasmon resonance
chip
Assay
transglycosylation
column chromatography

Software Mentioned

Biacore X100

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