Evidence map›Paper›PMID 29898782›Full record

ArticleJournal for immunotherapy of cancer2018

Expression of human CD46 and trans-complementation by murine adenovirus 1 fails to allow productive infection by a group B oncolytic adenovirus in murine cancer cells.

Janet Lei, Egon J Jacobus, William K Taverner, Kerry D Fisher, Silvio Hemmi, Katy West, Lorna Slater, Fred Lilley, Alice Brown, Brian Champion and 2 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Non-Human Primate-Derived Adenoviruses for Future Use as Oncolytic Agents?International journal of molecular sciences · 2020
    Review
  9. Article
  10. Article
  11. Review
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 at 3 institutions in 2 countries.

Janet Lei0000 0004 1936 8948grid.4991.5Department of OncologyUniversity of Oxford OX3 7DQ Oxford UK janet.lei@oncology.ox.ac.uk.
Egon J Jacobus0000 0004 1936 8948grid.4991.5Department of OncologyUniversity of Oxford OX3 7DQ Oxford UK egon.jacobus@oncology.ox.ac.uk.
William K Taverner0000 0004 1936 8948grid.4991.5Department of OncologyUniversity of Oxford OX3 7DQ Oxford UK william.taverner@dtc.ox.ac.uk.
Kerry D Fisher0000 0004 1936 8948grid.4991.5Department of OncologyUniversity of Oxford OX3 7DQ Oxford UK Kerry.fisher@oncology.ox.ac.uk.
Silvio Hemmi0000 0004 1937 0650grid.7400.3Institute of Molecular Life SciencesUniversity of Zurich Zurich Switzerland silvio.hemmi@imls.uzh.ch.
Katy West0000 0004 0394 8673grid.476643.4PsiOxus Therapeutics Ltd PsiOxus House, 4-10 The Quadrant, Barton Lane OX14 3YS Abingdon Oxfordshire UK katy.west@psioxus.com.
Lorna Slater0000 0004 0394 8673grid.476643.4PsiOxus Therapeutics Ltd PsiOxus House, 4-10 The Quadrant, Barton Lane OX14 3YS Abingdon Oxfordshire UK Lorna.slater@psioxus.com.
Fred Lilley0000 0004 0394 8673grid.476643.4PsiOxus Therapeutics Ltd PsiOxus House, 4-10 The Quadrant, Barton Lane OX14 3YS Abingdon Oxfordshire UK Fred.Lilley@psioxus.coms.
Alice Brown0000 0004 0394 8673grid.476643.4PsiOxus Therapeutics Ltd PsiOxus House, 4-10 The Quadrant, Barton Lane OX14 3YS Abingdon Oxfordshire UK Alice.Brown@psioxus.com.
Brian Champion0000 0004 0394 8673grid.476643.4PsiOxus Therapeutics Ltd PsiOxus House, 4-10 The Quadrant, Barton Lane OX14 3YS Abingdon Oxfordshire UK Brian.Champion@psioxus.com.
Margaret R Duffy0000 0004 1936 8948grid.4991.5Department of OncologyUniversity of Oxford OX3 7DQ Oxford UK Margaret.Duffy@oncology.ox.ac.uk.
Len W Seymour0000 0004 1936 8948grid.4991.5Department of OncologyUniversity of Oxford OX3 7DQ Oxford UK len.seymour@oncology.ox.ac.uk.ORCID http://orcid.org/0000-0003-3825-0841
University of Oxford · GBPsiOxus Therapeutics (United Kingdom) · GBUniversity of Zurich · CH

Funding

Cancer Research UK 17720Cancer Research UK C552/A17720
6 · The paper itself

Abstract

backgroundOncolytic viruses are currently experiencing accelerated development in several laboratories worldwide, with some forty-seven clinical trials currently recruiting. Many oncolytic viruses combine targeted cytotoxicity to cancer cells with a proinflammatory cell lysis. Due to their additional potential to express immunomodulatory transgenes, they are also often known as oncolytic viral vaccines. However, several types of oncolytic viruses are human-specific and the lack of suitable immune-competent animal models complicates biologically relevant evaluation of their vaccine potential. This is a particular challenge for group B adenoviruses, which fail to infect even those immunocompetent animal model systems identified as semi-permissive for type 5 adenovirus. Here, we aim to develop a murine cell line capable of supporting replication of a group B oncolytic adenovirus, enadenotucirev (EnAd), for incorporation into a syngeneic immunocompetent animal model to explore the oncolytic vaccine potential of group B oncolytic viruses.

methodsTransgenic murine cell lines were infected with EnAd expressing GFP transgene under replication-independent or -dependent promoters. Virus mRNA expression, genome replication, and late protein expression were determined by qRT-PCR, qPCR, and immunoblotting, respectively. We also use Balb/c immune-competent mice to determine the tumourogenicity and infectivity of transgenic murine cell lines.

resultsOur results show that a broad range of human carcinoma cells will support EnAd replication, but not murine carcinoma cells. Murine cells can be readily modified to express surface human CD46, one of the receptors for group B adenoviruses, allowing receptor-mediated uptake of EnAd particles into the murine cells and expression of CMV promoter-driven transgenes. Although the early E1A mRNA was expressed in murine cells at levels similar to human cells, adenovirus E2B and Fibre mRNA expression levels were hampered and few virus genomes were produced. Unlike previous reports on group C adenoviruses, trans-complementation of group B adenoviruses by co-infection with mouse adenovirus 1 did not rescue replication. A panel of group B adenoviruses expressing individual mouse adenovirus 1 genes were also unable to rescue EnAd replication.

conclusionTogether, these results indicate that there may be major differences in the early stages of replication of group C and B adenoviruses in murine cells, and that the block to the life cycle of B adenoviruses in murine cells occurs in the early stage of virus replication, perhaps reflecting poor activity of Ad11p E1A in murine cells.

Indexed as

AdenoviridaeAnimalsDisease Models, AnimalHumansMembrane Cofactor ProteinMiceMice, Inbred BALB CMice, TransgenicOncolytic VirotherapyMembrane Cofactor ProteinAdenovirus replicationGroup B adenovirusMouse modelOncolytic viruses

Identifiers

PMID29898782
PMCPMC6000980
OpenAlexW2807842720

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.