Evidence map›Paper›PMID 33682619›Full record

ArticlemAbs

Fc galactosylation follows consecutive reaction kinetics and enhances immunoglobulin G hexamerization for complement activation.

Bingchuan Wei, Xuan Gao, Lance Cadang, Saeed Izadi, Peilu Liu, Hui-Min Zhang, Elizabeth Hecht, Jeongsup Shim, Gordon Magill, Juan Rincon Pabon and 12 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
6.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
  2. Article
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  4. The glycan fingerprint in immune thrombocytopenia.Research and practice in thrombosis and haemostasis · 2026
    Article
  5. Article
  6. Review
  7. 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 · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 3 institutions in 1 country.

Bingchuan WeiProtein Analytical Chemistry, Genentech Inc., South San Francisco,United States.ORCID 0000-0003-1025-5579
Xuan GaoBiological Technologies, Genentech Inc., South San Francisco, United States.
Lance CadangProtein Analytical Chemistry, Genentech Inc., South San Francisco,United States.
Saeed IzadiPharmaceutical Development, Genentech Inc., South San Francisco, United States.ORCID 0000-0003-4206-8559
Peilu LiuProtein Analytical Chemistry, Genentech Inc., South San Francisco,United States.ORCID 0000-0002-0467-303X
Hui-Min ZhangProtein Analytical Chemistry, Genentech Inc., South San Francisco,United States.ORCID 0000-0002-2099-4730
Elizabeth HechtDepartment of Microchemistry, Proteomics and Lipidomics, Genentech Inc., South San Francisco, United States.
Jeongsup ShimBiological Technologies, Genentech Inc., South San Francisco, United States.ORCID 0000-0001-8390-9671
Gordon MagillDepartment of Cell Culture and Bioprocess Operations, Genentech Inc., South San Francisco, United States.
Juan Rincon PabonProtein Analytical Chemistry, Genentech Inc., South San Francisco,United States.
Lu DaiProtein Analytical Chemistry, Genentech Inc., South San Francisco,United States.
Wilson PhungDepartment of Microchemistry, Proteomics and Lipidomics, Genentech Inc., South San Francisco, United States.ORCID 0000-0001-7793-3931
Elaine LinBiological Technologies, Genentech Inc., South San Francisco, United States.
Christopher WangBiological Technologies, Genentech Inc., South San Francisco, United States.
Kevin WhangBiological Technologies, Genentech Inc., South San Francisco, United States.
Sean SanchezBiological Technologies, Genentech Inc., South San Francisco, United States.
Jose OropezaBiological Technologies, Genentech Inc., South San Francisco, United States.
Julien CamperiProtein Analytical Chemistry, Genentech Inc., South San Francisco,United States.ORCID 0000-0002-4020-2278
Jennifer ZhangProtein Analytical Chemistry, Genentech Inc., South San Francisco,United States.ORCID 0000-0002-9036-0477
Wendy SandovalDepartment of Microchemistry, Proteomics and Lipidomics, Genentech Inc., South San Francisco, United States.ORCID 0000-0002-4672-0762
Yonghua Taylor ZhangProtein Analytical Chemistry, Genentech Inc., South San Francisco,United States.
Guoying JiangBiological Technologies, Genentech Inc., South San Francisco, United States.ORCID 0000-0002-8059-0893
Protein Express (United States) · USFlorida State University · USUniversity of Kansas · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Protein Processing, Post-TranslationalAnimalsAntibodies, MonoclonalCHO CellsComplement ActivationComplement C1qCricetulusCytotoxicity, ImmunologicGalactoseImmunoglobulin Fc FragmentsImmunoglobulin GKineticsModels, BiologicalProtein MultimerizationStructure-Activity RelationshipAntibodies, MonoclonalComplement C1qGalactoseImmunoglobulin Fc FragmentsImmunoglobulin GCDC; CHO Cell CultureCQA; mass Spectrometrygalactosylationkineticsmonoclona antibody; IgG1

Identifiers

PMID33682619
PMCPMC7946005
OpenAlexW3134466524

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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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.