Preparation and biological activities of anti-HER2 monoclonal antibodies with fully core-fucosylated homogeneous bi-antennary complex-type glycans |
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| Authors: | Wataru Tsukimura Masaki Kurogochi Masako Mori Kenji Osumi Akio Matsuda Kaoru Takegawa |
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| Institution: | 1. Laboratory of Glyco-Bioengineering, The Noguchi Institute, Tokyo, Japan;2. Laboratory of Glyco-Organic Chemistry, The Noguchi Institute, Tokyo, Japan;3. Laboratory of Glyco-Organic Chemistry, The Noguchi Institute, Tokyo, Japan;4. Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan |
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| 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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| Keywords: | monoclonal antibodies N-glycans core-fucosylation ADCC activity therapeutic potential |
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