ArticleGene therapy2007
GCV modulates the antitumoural efficacy of a replicative adenovirus expressing the Tat8-TK as a late gene in a pancreatic tumour model.
Article in Gene therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Effect of Transgene Location, Transcriptional Control Elements and Transgene Features in Armed Oncolytic Adenoviruses.Cancers · 2020Review
- Translational reprogramming in tumour cells can generate oncoselectivity in viral therapies.Nature communications · 2017Article
- Codon optimization of the adenoviral fiber negatively impacts structural protein expression and viral fitness.Scientific reports · 2016Article
- Oncolytic virotherapy for urological cancers.Nature reviews. Urology · 2016Review
- Late-phase miRNA-controlled oncolytic adenovirus for selective killing of cancer cells.Oncotarget · 2015Article
- miR-148a- and miR-216a-regulated oncolytic adenoviruses targeting pancreatic tumors attenuate tissue damage without perturbation of miRNA activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts.Oncotarget · 2013Article
- GALV expression enhances the therapeutic efficacy of an oncolytic adenovirus by inducing cell fusion and enhancing virus distribution.Gene therapy · 2012Article
- Generation of a novel, cyclooxygenase-2-targeted, interferon-expressing, conditionally replicative adenovirus for pancreatic cancer therapy.American journal of surgery · 2012Article
- Selectivity and efficiency of late transgene expression by transcriptionally targeted oncolytic adenoviruses are dependent on the transgene insertion strategy.Human gene therapy · 2011Article
- Article
- E-cadherin contributes to the bystander effect of TK/GCV suicide therapy and enhances its antitumoral activity in pancreatic cancer models.Gene therapy · 2011Article
- Article
- Minimal RB-responsive E1A promoter modification to attain potency, selectivity, and transgene-arming capacity in oncolytic adenoviruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Hyaluronidase expression by an oncolytic adenovirus enhances its intratumoral spread and suppresses tumor growth.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- A modified E2F-1 promoter improves the efficacy to toxicity ratio of oncolytic adenoviruses.Gene therapy · 2009Article
- Imaging of viral thymidine kinase gene expression by replicating oncolytic adenovirus and prediction of therapeutic efficacy.Yonsei medical journal · 2008Article
- Syncytia formation affects the yield and cytotoxicity of an adenovirus expressing a fusogenic glycoprotein at a late stage of replication.Gene therapy · 2008Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication-competent adenoviruses carrying the herpes simplex thymidine kinase (TK) gene have shown contradictory evidence with regard to their antitumoural efficacy in combination with ganciclovir (GCV) treatment. We generated a replication-competent adenovirus carrying Tat8-TK, a modified form of the TK gene, under the control of the adenoviral major late promoter (AdRGDTat8-TK-L). Pancreatic cancer cell lines with different sensitivity to the TK/GCV system were infected with AdRGDTat8-TK-L, both in the presence and absence of GCV, and tested for treatment efficacy. We observed that, although the presence of GCV reduced viral replication in all infected cell lines, in three out of four GCV significantly enhanced the efficacy of the virotherapy. Interestingly, the cytotoxicity of the AdRGD-Tat8-TK-L/GCV was found more potent than that of a first generation AdTK/GCV system. In tumour xenografts from BxPC-3 and NP-18 pancreatic cells, both AdRGDTat8-TK-L and AdRGDTat8-TK-L/GCV treatment showed antitumoural activity. In BxPC-3 tumours scheduling of virus and prodrug was a key factor to determine the outcome of the therapy. Importantly, the addition of GCV enhanced the antitumoural effect of AdRGDTat8-TK-L only when applied in two rounds of virus+GCV. Interestingly, in spite of interfering with viral replication in vitro, GCV treatment of NP-18 tumours did not compromise the antitumoural efficacy of the AdRGDTat8-TK-L adenovirus. Thus, our results show that the combination therapy of a replicative adenovirus and the Tat8-TK/GCV suicide system can prove beneficial, when the appropriate regimen of virus and GCV is applied.
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