Evidence map›Paper›PMID 40204992›Full record

ArticleNature biomedical engineering2025

Site-directed multivalent conjugation of antibodies to ubiquitinated payloads.

Angela F El Hebieshy, Zacharias Wijfjes, Camille M Le Gall, Jim Middelburg, Kim E de Roode, Felix L Fennemann, Marjolein Sluijter, Thorbald van Hall, Douwe J Dijkstra, Leendert A Trouw and 15 more

Abstract read
In one paragraph

Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 2025 in review.Nature biomedical engineering · 2025
    Article
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

25 authors.

Angela F El Hebieshy *Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands. a.f.el_hebieshy@lumc.nl.ORCID http://orcid.org/0000-0002-1748-0368
Zacharias Wijfjes *Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0001-5705-1624
Camille M Le GallDepartment of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0002-5890-5115
Jim MiddelburgDepartment of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0002-4797-9653
Kim E de RoodeDepartment of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID http://orcid.org/0009-0009-6985-3507
Felix L FennemannDepartment of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Marjolein SluijterDepartment of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Thorbald van HallDepartment of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Douwe J DijkstraDepartment of Immunology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0002-2534-7575
Leendert A TrouwDepartment of Immunology, Leiden University Medical Center, Leiden, the Netherlands.
Floris J van DalenDepartment of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0002-2074-9794
Andrea Rodgers FuronesDepartment of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Johan M S van der SchootDepartment of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Ian DerksenDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
Hans de HaardArgenx BV, Gent, Belgium.
Bas van der WoningArgenx BV, Gent, Belgium.
Cami M P Talavera OrmeñoDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.
Bjorn R van DoodewaerdDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0001-9528-5587
Carl G FigdorDepartment of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0002-2366-9212
Gerbrand J van der Heden van NoortDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0001-5955-6431
Paul W H I ParrenDepartment of Immunology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0002-4365-3859
Sandra HeskampDepartment of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0001-7250-0846
Huib OvaaDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.
Martijn VerdoesDepartment of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands. m.verdoes1@lumc.nl.ORCID http://orcid.org/0000-0001-8753-3528
Ferenc A ScheerenDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands. f.a.scheeren@lumc.nl.ORCID http://orcid.org/0000-0002-8304-9023

Funding

Leids Universitair Medisch Centrum (Leiden University Medical Center) strategic fund
6 · The paper itself

Abstract

Antibody conjugates are the foundation of a wide range of diagnostic and therapeutic applications. Although many antibody-conjugation techniques are robust and efficient, obtaining homogeneous multimeric conjugation products remains challenging. Here we report a modular and versatile technique for the site-directed multivalent conjugation of antibodies via the small-protein ubiquitin. Specifically, multiple ubiquitin fusions with antibodies, antibody fragments, nanobodies, peptides or small molecules such as fluorescent dyes can be conjugated to antibodies and nanobodies within 30 min. The technique, which we named 'ubi-tagging', allowed us to efficiently generate a bispecific T-cell engager as well as nanobodies conjugated to dendritic-cell-targeted antigens that led to potent T-cell responses. Using both recombinant ubi-tagged proteins and synthetic ubiquitin derivatives allows for the iterative, site-directed and multivalent conjugation of antibodies and nanobodies to a plethora of molecular moieties.

Indexed as

AntibodiesImmunoconjugatesUbiquitinAnimalsDendritic CellsHumansMiceSingle-Domain AntibodiesT-LymphocytesUbiquitinationAntibodiesImmunoconjugatesSingle-Domain AntibodiesUbiquitin

Identifiers

PMID40204992
PMCPMC12270900

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.