Evidence map›Paper›PMID 25010337›Full record

ArticlePloS one2014

Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.

Raquel Garijo, Pablo Hernández-Alonso, Carmen Rivas, Jean-Simon Diallo, Rafael Sanjuán

Open access · goldAbstract 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 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed, 28 citations in OpenAlex.

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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

5 authors at 3 institutions in 2 countries.

Raquel GarijoInstituto Cavanilles de Biodiversidad y Biologia Evolutiva, Universidad de Valencia, Valencia, Spain; Center for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Pablo Hernández-AlonsoInstituto Cavanilles de Biodiversidad y Biologia Evolutiva, Universidad de Valencia, Valencia, Spain.
Carmen RivasDepartamento de Biología Molecular y Celular, Centro Nacional de Biotecnología, Madrid, Spain; Centro de Investigación en Medicina Molecular (CIMUS) and Instituto de Investigaciones Sanitarias (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Jean-Simon DialloCenter for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Rafael SanjuánInstituto Cavanilles de Biodiversidad y Biologia Evolutiva, Universidad de Valencia, Valencia, Spain; Department of Genetics, Universidad de Valencia, Valencia, Spain.
Ottawa Hospital Research InstituteUniversitat de València · ESInstituto de Investigación Sanitaria de Santiago · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hallmark of cancer cells. To achieve this goal, we established four independent evolution lines of the vesicular stomatitis virus (VSV) in p53-knockout mouse embryonic fibroblasts (p53-/- MEFs) under conditions favoring the action of natural selection. We found that some evolved viruses showed increased fitness and cytotoxicity in p53-/- cells but not in isogenic p53+/+ cells, indicating gene-specific adaptation. However, full-length sequencing revealed no obvious or previously described genetic changes associated with oncolytic activity. Half-maximal effective dose (EC50) assays in mouse p53-positive colon cancer (CT26) and p53-deficient breast cancer (4T1) cells indicated that the evolved viruses were more effective against 4T1 cells than the parental virus or a reference oncolytic VSV (MΔ51), but showed no increased efficacy against CT26 cells. In vivo assays using 4T1 syngeneic tumor models showed that one of the evolved lines significantly delayed tumor growth compared to mice treated with the parental virus or untreated controls, and was able to induce transient tumor suppression. Our results show that RNA viruses can be specifically adapted typical cancer features such as p53 inactivation, and illustrate the usefulness of experimental evolution for oncolytic virotherapy.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorColonic NeoplasmsDirected Molecular EvolutionFemaleHumansMiceMice, KnockoutOncolytic VirotherapyOncolytic VirusesTumor Suppressor Protein p53Vesicular StomatitisVesiculovirusTumor Suppressor Protein p53

Identifiers

PMID25010337
PMCPMC4092128
OpenAlexW2028624362

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.