Evidence map›Paper›PMID 33501689›Full record

ArticleBiotechnology and bioengineering2021

Use of 5-Thio-L-Fucose to modulate binding affinity of therapeutic proteins.

Martina Zimmermann, Melanie Nguyen, Christian M Schultheiss, Harald Kolmar, Aline Zimmer

Open access · hybridAbstract read
In one paragraph

Article in Biotechnology and bioengineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
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  4. A metabolic inhibitor blocks cellular fucosylation and enables production of afucosylated antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. Review
  6. Review
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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

5 authors at 2 institutions in 1 country.

Martina ZimmermannLife Science, Upstream R&D, Merck KGaA, Darmstadt, Germany.ORCID 0000-0001-5896-6084
Melanie NguyenLife Science, Upstream R&D, Merck KGaA, Darmstadt, Germany.ORCID 0000-0001-8439-047X
Christian M SchultheissLife Science, Upstream R&D, Merck KGaA, Darmstadt, Germany.ORCID 0000-0002-0696-9539
Harald KolmarInstitute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Darmstadt, Germany.ORCID 0000-0002-8210-1993
Aline ZimmerLife Science, Upstream R&D, Merck KGaA, Darmstadt, Germany.ORCID 0000-0003-0279-4863
Merck (Germany) · DETechnische Universität Darmstadt · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The reduction of antibody core-fucosylation is known to enhance antibody-dependent cellular cytotoxicity (ADCC). In this study, 5-Thio-l-Fucose (ThioFuc) was investigated as a media and feed supplement for modulating the fucosylation profile of therapeutic proteins and, thereby, improving the resulting effector functions. Glycan analysis of five different therapeutic proteins produced by a diverse set of Chinese hamster ovary cell lines demonstrated a clone dependent impact of ThioFuc treatment. Using rituximab as a model, an efficient dose- and time-dependent reduction of core-fucosylation up to a minimum of 5% were obtained by ThioFuc. Besides a concomitant increase in the afucosylation level up to 48%, data also revealed up to 47% incorporation of ThioFuc in place of core-fucosylation. In accordance with the glycan data, antibodies produced in the presence of ThioFuc revealed an enhanced FcγRIIIa binding up to 7.7-fold. Furthermore, modified antibodies subjected to a cell-based ADCC reporter bioassay proved to exert both a 1.5-fold enhanced ADCC efficacy and 2.6-fold enhancement in potency in comparison to their native counterparts-both of which contribute to an improvement in the ADCC activity. In conclusion, ThioFuc is a potent fucose derivative with potential applications in drug development processes.

Indexed as

BioreactorsReceptors, IgGRecombinant ProteinsAnimalsAntibody-Dependent Cell CytotoxicityCell Culture TechniquesCHO CellsCricetinaeCricetulusFucoseGlycosylationHumansProtein Binding5-thiofucoseFCGR3A protein, humanFucoseReceptors, IgGRecombinant Proteinsantibody-dependent cellular cytotoxicityCHO cell cultureFcγRIIIafucose analoguefucosylation

Identifiers

PMID33501689
PMCPMC8248388
OpenAlexW3125815075

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.