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

Wataru Tsukimura, Masaki Kurogochi, Masako Mori, Kenji Osumi, Akio Matsuda, Kaoru Takegawa, Kiyoshi Furukawa, Takashi Shirai

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2353-2359
Number of pages7
JournalBioscience, Biotechnology and Biochemistry
Volume81
Issue number12
DOIs
Publication statusPublished - Jan 1 2017

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Bioactivity
Polysaccharides
Monoclonal Antibodies
Cytotoxicity
Fucose
Fc Receptors
Blocking Antibodies
Antibodies
Immunoglobulin G

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

Cite this

Preparation and biological activities of anti-HER2 monoclonal antibodies with fully core-fucosylated homogeneous bi-antennary complex-type glycans. / Tsukimura, Wataru; Kurogochi, Masaki; Mori, Masako; Osumi, Kenji; Matsuda, Akio; Takegawa, Kaoru; Furukawa, Kiyoshi; Shirai, Takashi.

In: Bioscience, Biotechnology and Biochemistry, Vol. 81, No. 12, 01.01.2017, p. 2353-2359.

Research output: Contribution to journalArticle

Tsukimura, Wataru ; Kurogochi, Masaki ; Mori, Masako ; Osumi, Kenji ; Matsuda, Akio ; Takegawa, Kaoru ; Furukawa, Kiyoshi ; Shirai, Takashi. / Preparation and biological activities of anti-HER2 monoclonal antibodies with fully core-fucosylated homogeneous bi-antennary complex-type glycans. In: Bioscience, Biotechnology and Biochemistry. 2017 ; Vol. 81, No. 12. pp. 2353-2359.
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