ArticleCancer gene therapy2009
E1A, E1B double-restricted replicative adenovirus at low dose greatly augments tumor-specific suicide gene therapy for gallbladder cancer.
Article in Cancer gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
- A novel approach to glioma therapy using an oncolytic adenovirus with two specific promoters.Oncology letters · 2018Article
- Adenovirus-Mediated Gene Delivery: Potential Applications for Gene and Cell-Based Therapies in the New Era of Personalized Medicine.Genes & diseases · 2017Article
- Strategies and developments of immunotherapies in osteosarcoma.Oncology letters · 2016Article
- Progresses towards safe and efficient gene therapy vectors.Oncotarget · 2015Review
- Dissecting the roles of E1A and E1B in adenoviral replication and RCAd-enhanced RDAd transduction efficacy on tumor cells.Cancer biology & therapy · 2014Article
- Downregulation of Mcl-1 synergizes the apoptotic response to combined treatment with cisplatin and a novel fiber chimeric oncolytic adenovirus.Oncology reports · 2012Article
- Verapamil results in increased blood levels of oncolytic adenovirus in treatment of patients with advanced cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Intelligent design: combination therapy with oncolytic viruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Review
- Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combination therapy with replicative oncolytic viruses is a recent topic in innovative cancer therapy, but few studies have examined the efficacy of oncolytic adenovirus plus replication-deficient adenovirus carrying a suicide gene. We aim to evaluate whether an E1A, E1B double-restricted oncolytic adenovirus, AxdAdB-3, can improve the efficacy for gallbladder cancers (GBCs) of the replication-deficient adenovirus-based herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) therapy directed by the carcinoembryonic antigen (CEA) promoter. Cytopathic effects of AxdAdB-3 plus AxCEAprTK (an adenovirus expressing HSVtk directed by CEA promoter) or AxCAHSVtk (an adenovirus expressing HSVtk directed by a nonspecific CAG promoter) with GCV administration were examined in several GBC lines and normal cells. Efficacy in vivo was tested in severe combined immunodeficiency disease mice with GBC xenografts. Addition of AxdAdB-3 (1 multiplicity of infection, MOI) significantly enhanced the cytopathic effects of AxCEAprTK (10 MOI)/GCV on GBC cells. The augmented effect was attributable to the replication of the AxCEAprTK and also to the enhanced CEA promoter activity, which was presumably transactivated by E1A. In normal cells, AxdAdB-3 (20 MOI) plus AxCEAprTK (200 MOI)/GCV was not cytopathic, whereas AxdAdB-3 (1 MOI) plus AxCAHSVtk (10 MOI)/GCV was significantly toxic. Low-dose AxdAdB-3 (2 x 10(7) PFU, plaque-forming unit) plus AxCEAprTK (2 x 10(8) PFU)/GCV significantly suppressed the growth of GBC xenografts as compared with either AxdAdB-3 (2 x 10(7) PFU)/GCV or AxCEAprTK (2 x 10(9) PFU)/GCV alone. E1A, E1B double-restricted replicating adenovirus at low dose significantly augmented the efficacy of CEA promoter-directed HSVtk/GCV therapy without obvious toxicity to normal cells, suggesting a potential use of this combination for treating GBC and other CEA-producing malignancies.
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