Evidence map›Paper›PMID 25029910›Full record

ArticleArthritis research & therapy2014

Targeting of viral interleukin-10 with an antibody fragment specific to damaged arthritic cartilage improves its therapeutic potency.

Chris Hughes, Angelica Sette, Michael Seed, Fulvio D'Acquisto, Antonio Manzo, Tonia L Vincent, Ngee Han Lim, Ahuva Nissim

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  6. Targeting Cartilage Degradation in Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2021
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  14. The interrelation of osteoarthritis and diabetes mellitus: considering the potential role of interleukin-10 and in vitro models for further analysis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018
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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

8 authors at 4 institutions in 2 countries.

Chris Hughes
Angelica Sette
Michael Seed
Fulvio D'Acquisto
Antonio Manzo
Tonia L Vincent
Ngee Han Lim
Ahuva Nissim
Queen Mary University of London · GBIstituti di Ricovero e Cura a Carattere Scientifico · ITUniversity of East London · GBUniversity of Oxford · GB

Funding

Arthritis Research UK MP/18522Medical Research Council MR/J002747/1
6 · The paper itself

Abstract

introductionWe previously demonstrated that a single-chain fragment variable (scFv) specific to collagen type II (CII) posttranslationally modified by reactive oxygen species (ROS) can be used to target anti-inflammatory therapeutics specifically to inflamed arthritic joints. The objective of the present study was to demonstrate the superior efficacy of anti-inflammatory cytokines when targeted to inflamed arthritic joints by the anti-ROS modified CII (anti-ROS-CII) scFv in a mouse model of arthritis.

methodsViral interleukin-10 (vIL-10) was fused to anti-ROS-CII scFv (1-11E) with a matrix-metalloproteinase (MMP) cleavable linker to create 1-11E/vIL-10 fusion. Binding of 1-11E/vIL-10 to ROS-CII was determined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immune-staining of arthritic cartilage, whereas vIL-10 bioactivity was evaluated in vitro by using an MC-9 cell-proliferation assay. Specific in vivo localization and therapeutic efficacy of 1-11E/vIL-10 was tested in the mouse model of antigen-induced arthritis.

results1-11E/vIL-10 bound specifically to ROS-CII and to damaged arthritic cartilage. Interestingly, the in vitro vIL-10 activity in the fusion protein was observed only after cleavage with MMP-1. When systemically administered to arthritic mice, 1-11E/vIL-10 localized specifically to the arthritic knee, with peak accumulation observed after 3 days. Moreover, 1-11E/vIL-10 reduced inflammation significantly quicker than vIL-10 fused to the control anti-hen egg lysozyme scFv (C7/vIL10).

conclusionsTargeted delivery of anti-inflammatory cytokines potentiates their anti-arthritic action in a mouse model of arthritis. Our results further support the hypothesis that targeting biotherapeutics to arthritic joints may be extended to include anti-inflammatory cytokines that lack efficacy when administered systemically.

Indexed as

AnimalsAntibody SpecificityArthritis, ExperimentalBlotting, WesternCartilage, ArticularCollagen Type IIDrug Delivery SystemsEnzyme-Linked Immunosorbent AssayFemaleHumansImmunoglobulin Variable RegionImmunotherapyInterleukin-10MiceMice, Inbred C57BLReactive Oxygen SpeciesCollagen Type IIImmunoglobulin Variable RegionInterleukin-10Reactive Oxygen SpeciesRecombinant Fusion Proteins

Identifiers

PMID25029910
PMCPMC4225686
OpenAlexW2134519764

What OpenQuestion holds

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LicenceCC BY
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.