Cited by 372Monoclonal and Polyclonal Antibodies ResearchGlycosylation and Glycoproteins ResearchViral Infectious Diseases and Gene Expression in Insects

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

Kanda, Yutaka, Yamada, Tsuyoshi, Mori, Katsuhiro, Okazaki, Akira, Inoue, Miho, Kitajima-Miyama, Kazuko, Kuni-Kamochi, Reiko, Nakano, Ryosuke +4 more·2007·Glycobiology

Abstract

The structure of asparagine-linked oligosaccharides attached to the antibody constant region (Fc) of human immunoglobulin G1 (IgG1) has been shown to affect the pharmacokinetics and antibody effector functions of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, it is still unclear how differences in the N-linked oligosaccharide structures impact the biological activities of antibodies, especially those lacking core fucose. Here, we succeeded in generating core fucose-lacking human IgG1 antibodies with three different N-linked Fc oligosaccharides, namely, a high-mannose, hybrid, and complex type, using the same producing clone, and compared their activities. Cultivation of an alpha-1,6-fucosyltransferase (FUT8) knockout Chinese hamster ovary cell line in the presence or absence of a glycosidase inhibitor (either swainsonine or kifunensine) yielded antibody production of each of the three types without contamination by the others. Two of three types of nonnaturally occurring atypical oligosaccharide IgG1, except the complex type, reduced the affinity for both human lymphocyte receptor IIIa (FcgammaRIIIa) and the C1q component of the complement, resulting in reduction of ADCC and CDC. The bulky structure of the nonreducing end of N-linked Fc oligosaccharides is considered to contribute the CDC change, whereas the structural change in the reducing end, i.e. the removal of core fucose, causes ADCC enhancement through improved FcgammaRIIIa binding. In the pharmacokinetic profile, although no significant difference of human neonatal Fc receptor (FcRn)-binding affinity was observed among the three types, the complex type showed longer serum half-lives than the other types irrespective of core fucosylation in mice, which also suggests the contribution of the nonreducing end structure. The present study provides basic information on the effects of core fucose-lacking N-linked Fc oligosaccharides on antibody biological activities.

Integrity signals

Registry

Crossref · 10.1093/glycob/cwl057

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Kanda, Y., Yamada, T., Mori, K., Okazaki, A., Inoue, M., Kitajima-Miyama, K., Kuni-Kamochi, R., Nakano, R., Yano, K., Kakita, S., Shitara, K., & Satoh, M.
Venue
Glycobiology
Published
2006-09-29
Volume
17
Issue
1
Pages
104-118
ISSN
  • 0959-6658 (ISSN-L)
  • 1460-2423
OpenAlex
W2124847934
Cited by
372
References
48
Citations by year
2026: 8 · 2025: 9 · 2024: 16 · 2023: 21 · 2022: 12 · 2021: 30 · 2020: 13 · 2019: 20 · 2018: 29 · 2017: 21 · 2016: 36 · 2015: 26 · 2014: 20 · 2013: 17 · 2012: 22
FWCI
11.03
Type
journal article
Language
en
Open access
closed
Locations
  • Glycobiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
Keywords
IgG1 antibodies, Fc glycosylation, core fucose, N-glycans, complex types, antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, FcγRIIIa, C1q binding, FcRn binding, pharmacokinetics, swainsonine, kifunensine
MeSH terms
Rituximab, Animals, Antibodies, Monoclonal, Antibody-Dependent Cell Cytotoxicity, Carbohydrate Sequence, Complement System Proteins, Cricetulus, Cytotoxicity, Immunologic, Female, Fucosyltransferases, Cricetinae, Humans, Immunoglobulin G, Immunoglobulin Fc Fragments, Immunologic Factors, Mannans, Metabolic Clearance Rate, Molecular Sequence Data, Multiple Myeloma, Oligosaccharides, Protein Binding, Receptors, Fc, Structure-Activity Relationship, Histocompatibility Antigens Class I, Complement C1q, CHO Cells, Receptors, IgG, Organisms, Genetically Modified, Mice, Antibodies, Monoclonal, Murine-Derived

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review