Evidence map›Paper›PMID 12858190›Full record

ArticleGene therapy2003

Localized expression of an anti-TNF single-chain antibody prevents development of collagen-induced arthritis.

R Smith, I H Tarner, M Hollenhorst, C Lin, A U Levicnik, C G Fathman, G P Nolan

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

6 citing papers in PubMed, 30 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

R SmithBaxter Laboratory for Genetic Pharmacology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94304, USA.
I H Tarner
M Hollenhorst
C Lin
A U Levicnik
C G Fathman
G P Nolan
Stanford University · USBaxter (United States) · US

Funding

RETROVIRAL MEDIATED GENE THERAPY OF RHEUMATOID ARTHRITISN01AR062227 · NIAMS · STANFORD UNIVERSITY · PI FATHMAN, CHARLES GARRISON · 1996 to 2000
$528k
NIAMS NIH HHS N01-AR-62227
6 · The paper itself

Abstract

Although systemic administration of neutralizing anti-TNF antibodies has been used successfully in treating rheumatoid arthritis, there is a potential for side effects. We transduced a collagen reactive T-cell hybridoma with tissue-specific homing properties to assess therapeutic effects of local delivery to inflamed joints of anti-TNF single-chain antibodies (scFv) by adoptive cellular gene therapy. Cell culture medium conditioned with 1 x 10(6) scFv producer cells/ml had TNF neutralizing capacity in vitro equivalent to 50 ng/ml anti-TNF monoclonal antibody. Adding a kappa chain constant domain to the basic scFv (construct TN3-Ckappa) gave increased in vitro stability and in vivo therapeutic effect. TN3-Ckappa blocked development of collagen-induced arthritis in DBA/1LacJ mice for >60 days. Transgene expression was detected in the paws but not the spleen of treated animals for up to 55 days postinjection. No significant variations in cell proliferation or cytokine secretion were found in splenocytes or peripheral lymphocytes. IL-6 expression was blocked in the diseased paws of mice in the scFv treatment groups compared to controls. In conclusion, we have shown that local expression of an anti-inflammatory agent blocks disease development without causing demonstrable systemic immune function changes. This is encouraging for the potential development of safe adoptive cellular therapies to treat autoimmunity.

Indexed as

AnimalsAntibodies, MonoclonalArthritis, ExperimentalCells, CulturedCytokinesGene ExpressionGenetic TherapyGenetic VectorsLymph NodesMaleMiceMice, Inbred DBAMice, TransgenicRetroviridaeReverse Transcriptase Polymerase Chain ReactionSpleenAntibodies, MonoclonalCytokinesTumor Necrosis Factor-alpha

Identifiers

PMID12858190
OpenAlexW2019971607

What OpenQuestion holds

Textmetadata
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.