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- Title
Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
- Authors
Takashima, Shou; Kurogochi, Masaki; Tsukimura, Wataru; Mori, Masako; Osumi, Kenji; Sugawara, Shu-ichi; Amano, Junko; Mizuno, Mamoru; Takada, Yoshio; Matsuda, Akio
- Abstract
Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region. Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity. While the N -glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N -glycans may improve the efficacy of antibodies. The major glycoforms of the N -glycans on the IgG-Fc region are bi-antennary complex-type N -glycans, while multibranched complex-type N -glycans are not typically found. However, IgGs with tri-antennary complex-type N -glycans have been generated using the N -glycan remodeling technique, suggesting that more branched N -glycans might be artificially attached. At present, little is known about the properties of these IgGs. In this study, IgGs with multibranched N -glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N -glycan remodeling technique and successive reactions with glycosyltransferases. Among the IgGs produced by these methods, the largest N -glycan attached was a bisecting N -acetylglucosamine containing a sialylated penta-antennary structure. Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N -glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N -glycans.
- Subjects
IMMUNE response; MONOCLONAL antibodies; FC receptors; IMMUNOGLOBULIN G; ANTIBODY-dependent cell cytotoxicity; GLYCOSYLTRANSFERASES; IMMUNOGLOBULINS
- Publication
Glycobiology, 2021, Vol 31, Issue 10, p1401
- ISSN
0959-6658
- Publication type
Article
- DOI
10.1093/glycob/cwab064