Evidence map›Paper›PMID 12496961›Full record

ArticleNature medicine2003

Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways.

Wolfgang W Leitner, Leroy N Hwang, Michael J deVeer, Aimin Zhou, Robert H Silverman, Bryan R G Williams, Thomas W Dubensky, Han Ying, Nicholas P Restifo

Abstract read
In one paragraph

Article in Nature medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
6.5field-weighted citation impact, top 2% 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

105 citing papers in PubMed, 269 citations in OpenAlex.

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45 more citing papers are in PubMed but not listed here.

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 4 institutions in 1 country.

Wolfgang W LeitnerNational Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. wolfgang_leitner@nih.gov
Leroy N Hwang
Michael J deVeer
Aimin Zhou
Robert H Silverman
Bryan R G Williams
Thomas W Dubensky
Han Ying
Nicholas P Restifo
Cleveland Clinic · USNational Institutes of Health · USCleveland State University · USNational Cancer Institute · US

Funding

Building on the success of the adoptive immunotherapy of cancerZ01BC010763 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RESTIFO, NICHOLAS P · 2006 to 2008
$6.4M
REGULATION OF 2-5A-DEPENDENT RNASE LEVELS OF INTERFERONR01CA044059 · NCI · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI SILVERMAN, ROBERT H. · 1986 to 2015
$6.1M
REGULATION OF INTERFERON-INDUCED DSRNA-ACTIVATED KINASER01AI034039 · NIAID · MONASH UNIVERSITY · PI WILLIAMS, BRYAN R. G. · 1993 to 2008
$2.5M
Intramural NIH HHS Z01 BC010763Intramural NIH HHS Z99 CA999999NCI NIH HHS CA44059NCI NIH HHS R01 CA044059NIAID NIH HHS R01 AI034039NIAID NIH HHS R01-AI34039
6 · The paper itself

Abstract

Cancer vaccines targeting 'self' antigens that are expressed at consistently high levels by tumor cells are potentially useful in immunotherapy, but immunological tolerance may block their function. Here, we describe a novel, naked DNA vaccine encoding an alphavirus replicon (self-replicating mRNA) and the self/tumor antigen tyrosinase-related protein-1. Unlike conventional DNA vaccines, this vaccine can break tolerance and provide immunity to melanoma. The vaccine mediates production of double-stranded RNA, as evidenced by the autophosphorylation of dsRNA-dependent protein kinase R (PKR). Double-stranded RNA is critical to vaccine function because both the immunogenicity and the anti-tumor activity of the vaccine are blocked in mice deficient for the RNase L enzyme, a key component of the 2',5'-linked oligoadenylate synthetase antiviral pathway involved in double-stranded RNA recognition. This study shows for the first time that alphaviral replicon-encoding DNA vaccines activate innate immune pathways known to drive antiviral immune responses, and points the way to strategies for improving the efficacy of immunization with naked DNA.

Indexed as

Immune ToleranceMembrane GlycoproteinsOxidoreductasesAlphavirusAnimalsCancer VaccinesGenes, ReporterGene Transfer TechniquesHumansImmunizationImmunotherapyMelanomaMiceMice, Inbred C57BLPlasmidsProteinsCancer VaccinesMembrane GlycoproteinsOxidoreductasesProteinsRNA-Dependent RNA PolymeraseRNA, Double-Strandedtyrosinase-related protein-1TYRP1 protein, humanTyrp1 protein, mouseVaccines, DNA

Identifiers

PMID12496961
PMCPMC1484510
OpenAlexW1985491687

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.