Evidence map›Paper›PMID 34070311›Full record

ArticleCancers2021

Defucosylation of Tumor-Specific Humanized Anti-MUC1 Monoclonal Antibody Enhances NK Cell-Mediated Anti-Tumor Cell Cytotoxicity.

Ying Gong, Roel G J Klein Wolterink, Valeriia Gulaia, Silvie Cloosen, Femke A I Ehlers, Lotte Wieten, Yvo F Graus, Gerard M J Bos, Wilfred T V Germeraad

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Mucin Glycans: A Target for Cancer Therapy.Molecules (Basel, Switzerland) · 2023
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. 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

9 authors at 2 institutions in 2 countries.

Ying GongDepartment of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands.ORCID 0000-0001-5987-5344
Roel G J Klein WolterinkDepartment of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands.ORCID 0000-0001-6506-3270
Valeriia GulaiaDepartment of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands.ORCID 0000-0001-6826-6591
Silvie CloosenCiMaas BV, 6229 EV Maastricht, The Netherlands.
Femke A I EhlersDepartment of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands.ORCID 0000-0003-2272-6286
Lotte WietenGROW-School for Oncology and Developmental Biology, Maastricht University, 6229 GT Maastricht, The Netherlands.
Yvo F GrausCiMaas BV, 6229 EV Maastricht, The Netherlands.
Gerard M J BosDepartment of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands.
Wilfred T V GermeraadDepartment of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands.
Maastricht University · NLChampalimaud Foundation · PT

Funding

Cancer Research Institute/Irvington Postdoctoral Fellowship 100010434China Scholarship Council No. 201707720056Marie Skłodowska-Curie Individual fellowship 799810-TOPNINthe "la Caixa" Foundation LCF/BQ/PR20/11770004
6 · The paper itself

Abstract

Antibodies are commonly used in cancer immunotherapy because of their high specificity for tumor-associated antigens. The binding of antibodies can have direct effects on tumor cells but also engages natural killer (NK) cells via their Fc receptor. Mucin 1 (MUC1) is a highly glycosylated protein expressed in normal epithelial cells, while the under-glycosylated MUC1 epitope (MUC1-Tn/STn) is only expressed on malignant cells, making it an interesting diagnostic and therapeutic target. Several anti-MUC1 antibodies have been tested for therapeutic applications in solid tumors thus far without clinical success. Herein, we describe the generation of fully humanized antibodies based on the murine 5E5 antibody, targeting the tumor-specific MUC1-Tn/STn epitope. We confirmed that these antibodies specifically recognize tumor-associated MUC1 epitopes and can activate human NK cells in vitro. Defucosylation of these newly developed anti-MUC1 antibodies further enhanced antigen-dependent cellular cytotoxicity (ADCC) mediated by NK cells. We show that endocytosis inhibitors augment the availability of MUC1-Tn/STn epitopes on tumor cells but do not further enhance ADCC in NK cells. Collectively, this study describes novel fully humanized anti-MUC1 antibodies that, especially after defucosylation, are promising therapeutic candidates for cellular immunotherapy.

Indexed as

antibody-dependent cellular cytotoxicityantibody therapybreast cancerMUC1natural killer cells

Identifiers

PMID34070311
PMCPMC8197514
OpenAlexW3165223816

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.