Evidence map›Paper›PMID 25093639›Full record

ArticleHuman gene therapy2014

ORCA-010, a novel potency-enhanced oncolytic adenovirus, exerts strong antitumor activity in preclinical models.

Wenliang Dong, Jan-Willem H van Ginkel, Kam Y Au, Ramon Alemany, Janneke J M Meulenberg, Victor W van Beusechem

Open access · greenAbstract read
In one paragraph

Article in Human gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

25 citing papers in PubMed, 34 citations in OpenAlex.

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  15. Recent advances of oncolytic virus in cancer therapy.Human vaccines & immunotherapeutics · 2020
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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

6 authors at 3 institutions in 2 countries.

Wenliang Dong1 ORCA Therapeutics B.V. , 1081 HZ Amsterdam, The Netherlands .
Jan-Willem H van Ginkel
Kam Y Au
Ramon Alemany
Janneke J M Meulenberg
Victor W van Beusechem
AIMM Therapeutics (Netherlands) · NLAmsterdam UMC Location Vrije Universiteit Amsterdam · NLInstitut Català d'Oncologia · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Improving the antitumor potency of current oncolytic adenoviruses represents one of the major challenges in development of these viruses for clinical use. We have generated an oncolytic adenovirus carrying the safety-enhancing E1AΔ24 deletion, the potency-enhancing T1 mutation, and the infectivity-enhancing fiber RGD modification. The results of in vitro cytotoxicity assays on 15 human cancer cell lines derived from different tumor types demonstrated that ORCA-010 is more potent than Ad5-Δ24RGD or ONYX-015. As ORCA-010 will initially be developed for the treatment of prostate cancer, selectivity experiments were performed using primary human prostate cells. ORCA-010 killed cancer cells more effectively than these primary human cells. In both primary prostate fibroblasts and epithelial cells, ORCA-010 was as safe as Ad5-Δ24RGD. Evaluation of ORCA-010 in in vivo xenograft tumor models in nude mice showed that ORCA-010 significantly inhibited growth of prostate, lung, and ovarian tumors and conferred prolonged survival of tumor-bearing animals. Furthermore, we observed a substantial increase in infectious viral particles in tumors injected with ORCA-010. The number of infectious viral particles increased after treatment and infectious particles remained present up to at least 4 weeks posttreatment. Intratumoral virus replication was associated with substantial necrosis and fibrosis. In conclusion, ORCA-010 is more potent than earlier generation oncolytic adenoviruses, without demonstrating increased toxicity. ORCA-010 exerted strong in vivo antitumor activity and is therefore a suitable candidate for clinical evaluation.

Indexed as

Genetic TherapyOncolytic VirotherapyAdenoviruses, HumanAnimalsCell Line, TumorCytopathogenic Effect, ViralDisease Models, AnimalDrug Evaluation, PreclinicalGene OrderGenetic VectorsHumansMiceNeoplasmsOncolytic VirusesTumor BurdenVirus Replication

Identifiers

PMID25093639
PMCPMC4180126
OpenAlexW2322866056

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.