Evidence map›Paper›PMID 23604101›Full record

ArticleThe Journal of investigative dermatology2013

Therapeutic improvement of a stroma-targeted CRAd by incorporating motives responsive to the melanoma microenvironment.

Diego L Viale, Eduardo G Cafferata, David Gould, Cecilia Rotondaro, Yuti Chernajovsky, David T Curiel, Osvaldo L Podhajcer, M Veronica Lopez

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of investigative dermatology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Beyond cancer cells: Targeting the tumor microenvironment with gene therapy and armed oncolytic virus.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  8. Review
  9. Article
  10. Targeting Melanoma with Cancer-Killing Viruses.The open virology journal · 2017
    Article
  11. Article
  12. Article
  13. Enhanced CRAd activity using enhancer motifs driven by a nucleosome positioning sequence.Molecular therapy : the journal of the American Society of Gene Therapy · 2013
    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

8 authors at 3 institutions in 3 countries.

Diego L VialeLaboratory of Molecular and Cellular Therapy, Leloir Institute-CONICET, Buenos Aires, Argentina.
Eduardo G CafferataLaboratory of Molecular and Cellular Therapy, Leloir Institute-CONICET, Buenos Aires, Argentina.
David GouldBone and Joint Research Unit, University of London, London, UK.
Cecilia RotondaroLaboratory of Molecular and Cellular Therapy, Leloir Institute-CONICET, Buenos Aires, Argentina.
Yuti ChernajovskyBone and Joint Research Unit, University of London, London, UK.
David T CurielDivision of Human Gene Therapy, Departments of Medicine, Obstetrics and Gynecology, Pathology and Surgery, Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama, USA; Biologic Therapeutics Center, Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri, USA.
Osvaldo L PodhajcerLaboratory of Molecular and Cellular Therapy, Leloir Institute-CONICET, Buenos Aires, Argentina. Electronic address: opodhajcer@leloir.org.ar.
M Veronica LopezLaboratory of Molecular and Cellular Therapy, Leloir Institute-CONICET, Buenos Aires, Argentina. Electronic address: mlopez@leloir.org.ar.
Consejo Nacional de Investigaciones Científicas y Técnicas · ARUniversity of London · GBWashington University in St. Louis · US

Funding

UAB / UMN SPORE in Pancreatic CancerP50CA101955 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BUCHSBAUM, DONALD J · 2010 to 2014
$11.1M
NCI NIH HHS P50 CA101955
6 · The paper itself

Abstract

We have previously designed a conditionally replicative oncolytic adenovirus (CRAd) named Ad-F512 that can target both the stromal and the malignant melanoma cell compartments. The replication capacity of this CRAd is driven by a 0.5-Kb SPARC promoter fragment (named F512). To improve CRAd's efficacy, we cloned into F512 motives responsive to hypoxia (hypoxia-responsive element (HRE)) and inflammation (nuclear factor kappa B) to obtain a chimeric promoter named κBF512HRE. Using luciferase as a reporter gene, we observed 10-15-fold increased activity under hypoxia and 10-80-fold induction upon tumor necrosis factor-α addition. We next constructed a CRAd (Ad-κBF512HRE) where E1A activity was under κBF512HRE regulation. Treatment of nude mice harboring established tumors made of a mix of SB2 melanoma cells and WI-38 fibroblasts with Ad-κBF512HRE led to the complete elimination of tumors in 100% of mice (8/8). Moreover, Ad-5/3-κBF512HRE, a viral variant pseudotyped with a chimeric 5/3 fiber, exerted a strong lytic effect on CAR-negative melanoma cells and was highly effective in vivo on established tumors made of melanoma cells and WI-38 fibroblasts, leading to the complete elimination of 4/5 tumors. These results indicate that this improved stroma-targeted oncolytic adenovirus can override the resistance of melanoma tumors and might become of significant importance for melanoma therapeutics.

Indexed as

AdenoviridaeAnimalsCell Line, TumorFibroblastsHEK293 CellsHumansMaleMelanomaMiceMice, NudeOncolytic VirotherapyPromoter Regions, GeneticSkin NeoplasmsStromal CellsTumor MicroenvironmentXenograft Model Antitumor Assays

Identifiers

PMID23604101
PMCPMC4159097
OpenAlexW2094858550

What OpenQuestion holds

Textmetadata
LicenceTDM
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.