Evidence map›Paper›PMID 12552003›Full record

ArticleJournal of virology2003

Developing novel oncolytic adenoviruses through bioselection.

Wen Yan, Galila Kitzes, Farid Dormishian, Lynda Hawkins, Adam Sampson-Johannes, Josh Watanabe, Jenny Holt, Vivian Lee, Thomas Dubensky, Ali Fattaey and 3 more

Open access · greenAbstract readEvaluation Study
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

26 citing papers in PubMed, 54 citations in OpenAlex.

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  16. Adenovirus i-leader truncation bioselected against cancer-associated fibroblasts to overcome tumor stromal barriers.Molecular therapy : the journal of the American Society of Gene Therapy · 2012
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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

13 authors.

Wen YanONYX Pharmaceuticals, Inc., 3031 Research Drive, Richmond, CA 94806, USA.
Galila Kitzes
Farid Dormishian
Lynda Hawkins
Adam Sampson-Johannes
Josh Watanabe
Jenny Holt
Vivian Lee
Thomas Dubensky
Ali Fattaey
Terry Hermiston
Allan Balmain
Yuqiao Shen

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mutants of human adenovirus 5 (Ad5) with enhanced oncolytic activity were isolated by using a procedure termed bioselection. Two mutants, ONYX-201 and ONYX-203, were plaque purified from a pool of randomly mutagenized Ad5 that was repeatedly passaged in the human colorectal cancer cell line HT29, and they were subsequently characterized. ONYX-201 and ONYX-203 replicated more rapidly in HT29 cells than wild-type Ad5, and they lysed HT29 cells up to 1,000-fold more efficiently. The difference was most profound when cells were infected at a relatively low multiplicity of infection, presumably due to the compounding effects of multiple rounds of infection. This enhanced cytolytic activity was observed not only in HT29 cells but also in many other human cancer cell lines tested. In contrast, the cytotoxicity of the bioselected mutants in a number of normal primary human cells was similar to that of wild-type Ad5, thus enhancing the therapeutic index (cytotoxicity in tumor cells versus that in normal cells) of these oncolytic agents. Both ONYX-201 and -203 contain seven single-base-pair mutations when compared with Ad5, four of which were common between ONYX-201 and -203. The mutation at nucleotide 8350, shared by both mutant viruses, was shown to be essential for the observed phenotypes. This mutation was mapped to the i-leader region of the major late transcription unit, resulting in the truncation of 21 amino acids from the C terminus of the i-leader protein. This work demonstrates that bioselection is a powerful tool for developing novel tumor-selective oncolytic viruses. Other potential applications of this technology are discussed.

Indexed as

Selection, GeneticAdenoviruses, HumanCytopathogenic Effect, ViralHumansMutagenesisSerial PassageTumor Cells, CulturedVirologyVirus Replication

Identifiers

PMID12552003
PMCPMC141112
OpenAlexW2106503298

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.