ArticlemAbs
Fc galactosylation follows consecutive reaction kinetics and enhances immunoglobulin G hexamerization for complement activation.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Review
- Experimental and computational analysis of glycan processing at increased monoclonal antibody productivities.Metabolic engineering communications · 2026Article
- Antigen-specific IgG glycosylation profiles in hamsters and macaques following COVID-19 vaccination.iScience · 2026Article
- The glycan fingerprint in immune thrombocytopenia.Research and practice in thrombosis and haemostasis · 2026Article
- Causal associations of specific immunoglobulin G N-glycosylation subtypes with osteoporosis: A two-sample Mendelian randomization.Joint diseases and related surgery · 2026Article
- N-Glycosylation of Antibodies: Biological Effects During Infections and Therapeutic Applications.Antibodies (Basel, Switzerland) · 2025Review
- Exploring glycoform-dependent dynamic modulations in human immunoglobulin G via computational and experimental approaches.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Modulation of immunoglobulin G oligomerization by variable domain glycans: A mechanism to regulate complement activation.PNAS nexus · 2025Article
- Article
- Review
- IgG1 glycosylation highlights premature aging in Down syndrome.Aging cell · 2024Article
- N-linked Fc glycosylation is not required for IgG-B-cell receptor function in a GC-derived B-cell line.Nature communications · 2024Article
- Reduced serum IgG galactosylation is associated with increased inflammation during relapses of neuromyelitis optica spectrum disorders.Frontiers in immunology · 2024Article
- Article
- The unique properties of IgG4 and its roles in health and disease.Nature reviews. Immunology · 2023Review
- Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines.iScience · 2023Article
- Long-Term Culturing of FreeStyle 293-F Cells Affects Immunoglobulin G Glycome Composition.Biomolecules · 2023Article
- Effect of posttranslational modifications and subclass on IgG activity: from immunity to immunotherapy.Nature immunology · 2023Review
- The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees.EBioMedicine · 2023Article
- Factors affecting IgG4-mediated complement activation.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fc galactosylation is a critical quality attribute for anti-tumor recombinant immunoglobulin G (IgG)-based monoclonal antibody (mAb) therapeutics with complement-dependent cytotoxicity (CDC) as the mechanism of action. Although the correlation between galactosylation and CDC has been known, the underlying structure-function relationship is unclear. Heterogeneity of the Fc N-glycosylation produced by Chinese hamster ovary (CHO) cell culture biomanufacturing process leads to variable CDC potency. Here, we derived a kinetic model of galactose transfer reaction in the Golgi apparatus and used this model to determine the correlation between differently galactosylated species from CHO cell culture process. The model was validated by a retrospective data analysis of more than 800 historical samples from small-scale and large-scale CHO cell cultures. Furthermore, using various analytical technologies, we discovered the molecular basis for Fc glycan terminal galactosylation changing the three-dimensional conformation of the Fc, which facilitates the IgG1 hexamerization, thus enhancing C1q avidity and subsequent complement activation. Our study offers insight into the formation of galactosylated species, as well as a novel three-dimensional understanding of the structure-function relationship of terminal galactose to complement activation in mAb therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.