Evidence map›Paper›PMID 41965429›Full record

ArticleCommunications biology2026

Glycan-based biological degraders targeting the cytokine immune axis.

Michelle Seifert, Tim Kollenkirchen, Andreas Ernst, Samaneh Rasoulinejad, Sarah M S Koellner, Ann-Kathrin Schneider, Marcin Luzarowski, Nicole Lübbehusen, Di Wu, Aimo Kannt and 1 more

Abstract read
In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Michelle SeifertFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany.
Tim KollenkirchenFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany.
Andreas ErnstFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany.
Samaneh RasoulinejadFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany.
Sarah M S KoellnerFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany.
Ann-Kathrin SchneiderFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany.
Marcin LuzarowskiCore Facility for Mass Spectrometry and Proteomics, Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.
Nicole LübbehusenCore Facility for Mass Spectrometry and Proteomics, Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.
Di WuFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany.
Aimo KanntFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany.ORCID http://orcid.org/0000-0002-5197-2286
Schara SafarianFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany. schara.safarian@itmp.fraunhofer.de.ORCID http://orcid.org/0000-0002-0232-1612

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeted degradation of extracellular proteins via endo-lysosomal pathways constitutes a promising therapeutic strategy by enabling irreversible target removal and potentially reducing systemic effects of antigen accumulation. In this study, we present a systematic approach for the design and evaluation of Biological Degraders (BioDegs) that leverage receptor-mediated uptake through triantennary N-acetylgalactosamine (TGN) induced activation of the asialoglycoprotein receptor (ASGPR). While this principle has been established, there is still a lack about molecular determinants that influence uptake efficiency. Using interleukin-6 (IL-6) and its soluble receptor (sIL-6R) as therapeutically relevant model antigens, we systematically compared a range of BioDeg formats, including full-length antibodies (siltuximab, tocilizumab), a VHH against IL-6, and an IL-6 binding decoy-receptor design, with respect to binding affinity, thermal stability, cellular uptake, lysosomal trafficking, and degradation efficiency in HepG2 cells. Our results demonstrate that combined properties of scaffold architecture and receptor engagement critically influence degradation outcomes. This work provides a comparative framework for BioDeg design and highlights key parameters for developing lysosome-targeting degraders for extracellular proteins.

Indexed as

CytokinesInterleukin-6PolysaccharidesAsialoglycoprotein ReceptorHep G2 CellsHumansLysosomesProteolysisReceptors, Interleukin-6Asialoglycoprotein ReceptorCytokinesInterleukin-6PolysaccharidesReceptors, Interleukin-6

Identifiers

PMID41965429
PMCPMC13083842

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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.