ArticleProceedings of the National Academy of Sciences of the United States of America2015
Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 132 papers, 1 of them a synthesis that pooled it.
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Who cites it
132 citing papers in PubMed, 1 synthesis or guideline pooled it, 224 citations in OpenAlex.
- Glycosylation of Immunoglobulin G Associates With Clinical Features of Inflammatory Bowel Diseases.Gastroenterology · 2018Pooled it
- Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity.The Journal of clinical investigation · 2015Trial
- IgM Hyposialylation Modulates Podocyte Vulnerability in Patients With Idiopathic Nephrotic Syndrome.Kidney international reports · 2026Article
- Inhibiting glycan degradation prevents HIV-induced inflammaging and cognitive impairment.Med (New York, N.Y.) · 2026Article
- Inhibiting Glycan Degradation Prevents HIV-Induced Inflammaging and Cognitive Impairment.bioRxiv : the preprint server for biology · 2025Article
- The anti-inflammatory activity of IgG is enhanced by co-engagement of type I and II Fc receptors.Science (New York, N.Y.) · 2025Article
- Multivariate analysis of glycogenes reveals coordinated regulation of immunoglobulin glycosylation in an immortalized human B cell system.bioRxiv : the preprint server for biology · 2025Article
- Estrogen Modulation of B Cell Immunity: Implications for HIV Control and Therapeutic Strategies.Comprehensive physiology · 2025Review
- Molecular determinants of sialylated IgG anti-inflammatory activity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Glycosylation as an intricate post-translational modification process takes part in glycoproteins related immunity.Cell communication and signaling : CCS · 2025Review
- Soluble Factors and Mechanisms Regulated by Sialylated IgG Signaling.Immunological reviews · 2025Review
- Role of Antibody Glycosylation in Health, Disease, and Therapy.Handbook of experimental pharmacology · 2025Review
- Antibody-mediated control mechanisms of viral infections.Immunological reviews · 2024Review
- The role of antibody glycosylation in autoimmune and alloimmune kidney diseases.Nature reviews. Nephrology · 2024Review
- Emerging treatment landscape for Guillain-Barré Syndrome (GBS): what's new?Expert opinion on investigational drugs · 2024Review
- Immunoglobulin G glycosylation and its alterations in aging-related diseases.Acta biochimica et biophysica Sinica · 2024Review
- GlYcoLISA: antigen-specific and subclass-specific IgG Fc glycosylation analysis based on an immunosorbent assay with an LC-MS readout.Nature protocols · 2024Review
- Immobilized enzyme cascade for targeted glycosylation.Nature chemical biology · 2024Article
- Local Immune Activation and Age Impact on Humoral Immunity in Mice, with a Focus on IgG Sialylation.Vaccines · 2024Article
- Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection.Nature communications · 2024Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the beneficial therapeutic effects of intravenous immunoglobulin (IVIg) in inflammatory diseases, consistent therapeutic efficacy and potency remain major limitations for patients and physicians using IVIg. These limitations have stimulated a desire to generate therapeutic alternatives that could leverage the broad mechanisms of action of IVIg while improving therapeutic consistency and potency. The identification of the important anti-inflammatory role of fragment crystallizable domain (Fc) sialylation has presented an opportunity to develop more potent Ig therapies. However, translating this concept to potent anti-inflammatory therapeutics has been hampered by the difficulty of generating suitable sialylated products for clinical use. Therefore, we set out to develop the first, to our knowledge, robust and scalable process for generating a well-qualified sialylated IVIg drug candidate with maximum Fc sialylation devoid of unwanted alterations to the IVIg mixture. Here, we describe a controlled enzymatic, scalable process to produce a tetra-Fc-sialylated (s4-IVIg) IVIg drug candidate and its qualification across a wide panel of analytic assays, including physicochemical, pharmacokinetic, biodistribution, and in vivo animal models of inflammation. Our in vivo characterization of this drug candidate revealed consistent, enhanced anti-inflammatory activity up to 10-fold higher than IVIg across different animal models. To our knowledge, this candidate represents the first s4-IVIg suitable for clinical use; it is also a valuable therapeutic alternative with more consistent and potent anti-inflammatory activity.
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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.