Evidence map›Paper›PMID 24760010›Full record

ArticlePloS one2014

Adenoviruses using the cancer marker EphA2 as a receptor in vitro and in vivo by genetic ligand insertion into different capsid scaffolds.

Michael Behr, Johanna K Kaufmann, Patrick Ketzer, Sarah Engelhardt, Martin Mück-Häusl, Pamela M Okun, Gabriele Petersen, Frank Neipel, Jessica C Hassel, Anja Ehrhardt and 2 more

Abstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
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  8. Article
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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

12 authors.

Michael BehrOncolytic Adenovirus Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Johanna K KaufmannOncolytic Adenovirus Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Patrick KetzerOncolytic Adenovirus Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Sarah EngelhardtOncolytic Adenovirus Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Martin Mück-HäuslMax von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University Munich, Munich, Germany.
Pamela M OkunDepartment of General Pediatrics, Division of Inherited Metabolic Diseases, Heidelberg University Hospital, Heidelberg, Germany.
Gabriele PetersenCOS, CellNetworks Deep Sequencing Core Facility, University Heidelberg, Heidelberg, Germany.
Frank NeipelInstitute for Clinical and Molecular Virology, Erlangen University Hospital, Erlangen, Germany.
Jessica C HasselDepartment of Dermatology, Heidelberg University Hospital, Heidelberg, Germany.
Anja EhrhardtMax von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University Munich, Munich, Germany; Institute of Virology and Microbiology, Center for Biomedical Education and Research, Department of Human Medicine, Faculty of Health, University Witten/Herdecke, Witten, Germany.
Alexander H EnkDepartment of Dermatology, Heidelberg University Hospital, Heidelberg, Germany.
Dirk M NettelbeckOncolytic Adenovirus Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adenoviral gene therapy and oncolysis would critically benefit from targeted cell entry by genetically modified capsids. This requires both the ablation of native adenovirus tropism and the identification of ligands that remain functional in virus context. Here, we establish cell type-specific entry of HAdV-5-based vectors by genetic ligand insertion into a chimeric fiber with shaft and knob domains of the short HAdV-41 fiber (Ad5T/41sSK). This fiber format was reported to ablate transduction in vitro and biodistribution to the liver in vivo. We show that the YSA peptide, binding to the pan-cancer marker EphA2, can be inserted into three positions of the chimeric fiber, resulting in strong transduction of EphA2-positive but not EphA2-negative cells of human melanoma biopsies and of tumor xenografts after intratumoral injection. Transduction was blocked by soluble YSA peptide and restored for EphA2-negative cells after recombinant EphA2 expression. The YSA peptide could also be inserted into three positions of a CAR binding-ablated HAdV-5 fiber enabling specific transduction; however, the Ad5T/41sSK format was superior in vivo. In conclusion, we establish an adenovirus capsid facilitating functional insertion of targeting peptides and a novel adenovirus using the tumor marker EphA2 as receptor with high potential for cancer gene therapy and viral oncolysis.

Indexed as

AdenoviridaeAnimalsCell LineFemaleHumansMelanomaMiceMice, Inbred NODMice, SCIDReceptor, EphA2Xenograft Model Antitumor AssaysReceptor, EphA2

Identifiers

PMID24760010
PMCPMC3997477

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.