Evidence map›Paper›PMID 26034897›Full record

ArticleGene therapy2015

Treatment of multifocal breast cancer by systemic delivery of dual-targeted adeno-associated viral vectors.

M Trepel, J Körbelin, E Spies, M B Heckmann, A Hunger, B Fehse, H A Katus, J A Kleinschmidt, O J Müller, S Michelfelder

Erratum issuedOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Lung endothelial cytopathic tau is sufficient to impair long-term potentiation during infection.American journal of respiratory cell and molecular biology · 2026
    Article
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  5. Review
  6. Review
  7. Review
  8. Article
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  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Peptide-Based Supramolecular Hydrogels for Delivery of Biologics.Bioengineering & translational medicine · 2016
    Article
  17. MicroRNA-regulated viral vectors for gene therapy.World journal of experimental medicine · 2016
    Review
  18. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 1 country.

M TrepelDepartment of Oncology and Hematology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistr, Hamburg, Germany.
J KörbelinDepartment of Oncology and Hematology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistr, Hamburg, Germany.
E SpiesDepartment of Oncology and Hematology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistr, Hamburg, Germany.
M B HeckmannUniversity Hospital Heidelberg, Heidelberg, and DZHK (German Center for Cardiovascular Research), partner site Heidelberg/Mannheim, Im Neuenheimer Feld 410, Heidelberg, Germany.
A HungerDepartment of Oncology and Hematology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistr, Hamburg, Germany.
B FehseDepartment of Cell and Gene Therapy, Bone Marrow Transplantation Unit Research, University Medical Center Hamburg-Eppendorf, Martinistr, Hamburg, Germany.
H A KatusUniversity Hospital Heidelberg, Heidelberg, and DZHK (German Center for Cardiovascular Research), partner site Heidelberg/Mannheim, Im Neuenheimer Feld 410, Heidelberg, Germany.
J A KleinschmidtDeutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, Heidelberg, Germany.
O J MüllerUniversity Hospital Heidelberg, Heidelberg, and DZHK (German Center for Cardiovascular Research), partner site Heidelberg/Mannheim, Im Neuenheimer Feld 410, Heidelberg, Germany.
S MichelfelderDepartment of Oncology and Hematology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistr, Hamburg, Germany.
Heidelberg University · DEUniversität Hamburg · DEUniversity Cancer Center Hamburg · DEDKFZ-ZMBH Alliance · DEUniversity Medical Center Hamburg-Eppendorf · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adeno-associated viral (AAV) vectors yield high potential for clinical gene therapy but, like for other vectors systems, they frequently do not sufficiently transduce the target tissue and their unspecific tropism prevents their application for multifocal diseases such as disseminated cancer. Targeted AAV vectors have been obtained from random AAV display peptide libraries but so far, all vector variants selected from AAV libraries upon systemic administration in vivo retained some collateral tropism, frequently the heart. Here we explored, if this impediment can be overcome by microRNA-regulated transgene cassettes as the combination of library-derived capsid targeting and micro-RNA control has not been evaluated so far. We used a tumor-targeted AAV capsid variant (ESGLSQS) selected from random AAV-display peptide libraries in vivo with remaining off-target tropism toward the heart and regulated targeted transgene expression in vivo by complementary target elements for heart-specific microRNA (miRT-1d). Although this vector still maintained its strong transduction capacity for tumor target tissue after intravenous injection, transgene expression in the heart was almost completely abrogated. This strong and completely tumor-specific transgene expression was used for therapeutic gene transfer in an aggressive multifocal, transgenic, polyoma middle T-induced, murine breast cancer model. A therapeutic suicide gene, delivered systemically by this dual-targeted AAV vector to multifocal breast cancer, significantly inhibited tumor growth after one single vector administration while avoiding side effects compared with untargeted vectors.

Indexed as

DependovirusGenes, Transgenic, SuicideGenetic TherapyGenetic VectorsAnimalsFemaleMammary Neoplasms, ExperimentalMiceMicroRNAsMicroRNAs

Identifiers

PMID26034897
OpenAlexW837049827

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.