Evidence map›Paper›PMID 24503218›Full record

ArticleMolecular oncology2014

Preclinical study on combined chemo- and nonviral gene therapy for sensitization of melanoma using a human TNF-alpha expressing MIDGE DNA vector.

Dennis Kobelt, Jutta Aumann, Manuel Schmidt, Burghardt Wittig, Iduna Fichtner, Diana Behrens, Margit Lemm, Greta Freundt, Peter M Schlag, Wolfgang Walther

Open access · bronzeAbstract read
In one paragraph

Article in Molecular oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% 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, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Advanced Design of Dumbbell-shaped Genetic Minimal Vectors Improves Non-coding and Coding RNA Expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Article
  6. 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

10 authors at 3 institutions in 1 country.

Dennis KobeltMax-Delbrück-Center for Molecular Medicine, Berlin, Germany. Electronic address: dennis.kobelt@mdc-berlin.de.
Jutta AumannMax-Delbrück-Center for Molecular Medicine, Berlin, Germany; Experimental and Clinical Research Center, Charité University Medicine, Berlin, Germany.
Manuel SchmidtMologen AG, Berlin, Germany.
Burghardt WittigFoundation Institute Molecular Biology and Bioinformatics, Freie Universität Berlin, Berlin, Germany.
Iduna FichtnerMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Diana BehrensMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Margit LemmMax-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Greta FreundtMax-Delbrück-Center for Molecular Medicine, Berlin, Germany; Experimental and Clinical Research Center, Charité University Medicine, Berlin, Germany.
Peter M SchlagMax-Delbrück-Center for Molecular Medicine, Berlin, Germany; Charité Comprehensive Cancer Center, Berlin, Germany.
Wolfgang WaltherMax-Delbrück-Center for Molecular Medicine, Berlin, Germany; Experimental and Clinical Research Center, Charité University Medicine, Berlin, Germany. Electronic address: wowalt@mdc-berlin.de.
Max Delbrück Center · DEFreie Universität Berlin · DEMologen (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nonviral gene therapy represents a realistic option for clinical application in cancer treatment. This preclinical study demonstrates the advantage of using the small-size MIDGE(®) DNA vector for improved transgene expression and therapeutic application. This is caused by significant increase in transcription efficiency, but not by increased intracellular vector copy numbers or gene transfer efficiency. We used the MIDGE-hTNF-alpha vector for high-level expression of hTNF-alpha in vitro and in vivo for a combined gene therapy and vindesine treatment in human melanoma models. The MIDGE vector mediated high-level hTNF-alpha expression leads to sensitization of melanoma cells towards vindesine. The increased efficacy of this combination is mediated by remarkable acceleration and increase of initiator caspase 8 and 9 and effector caspase 3 and 7 activation. In the therapeutic approach, the nonviral intratumoral in vivo jet-injection gene transfer of MIDGE-hTNF-alpha in combination with vindesine causes melanoma growth inhibition in association with increased apoptosis in A375 cell line or patient derived human melanoma xenotransplant (PDX) models. This study represents a proof-of-concept for an anticipated phase I clinical gene therapy trial, in which the MIDGE-hTNF-alpha vector will be used for efficient combined chemo- and nonviral gene therapy of malignant melanoma.

Indexed as

AnimalsAntineoplastic Agents, PhytogenicCell Line, TumorDNAFemaleGenetic TherapyGenetic VectorsHumansMelanomaMiceTransfectionTransgenesTumor Necrosis Factor-alphaVindesineAntineoplastic Agents, PhytogenicDNATumor Necrosis Factor-alphaVindesineCancerGene therapyMelanomaNonviral gene transferTNF-alpha

Identifiers

PMID24503218
PMCPMC5528640
OpenAlexW1971577502

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.