ArticleJournal of virology2010
A novel bicistronic high-capacity gutless adenovirus vector that drives constitutive expression of herpes simplex virus type 1 thymidine kinase and tet-inducible expression of Flt3L for glioma therapeutics.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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.
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.
Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- The promise of immunotherapy for central nervous system tumours.Nature reviews. Immunology · 2026Review
- Promising Cancer Vaccine for Glioblastoma Therapy: A Focus on mRNA Vaccine.Cancer medicine · 2025Review
- Cell and gene therapy in neuro-oncology.Handbook of clinical neurology · 2024Review
- Targeting FOXP3 Tumor-Intrinsic Effects Using Adenoviral Vectors in Experimental Breast Cancer.Viruses · 2023Article
- Review
- Effects of oncolytic viruses and viral vectors on immunity in glioblastoma.Gene therapy · 2022Review
- Advances in immunotherapy for glioblastoma multiforme.Frontiers in immunology · 2022Review
- Role of Adenoviruses in Cancer Therapy.Frontiers in oncology · 2022Review
- Current Approaches for Glioma Gene Therapy and Virotherapy.Frontiers in molecular neuroscience · 2021Review
- High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy.International journal of molecular sciences · 2020Review
- Viral vector: potential therapeutic for glioblastoma multiforme.Cancer gene therapy · 2020Review
- Preclinical Evaluation of a Replication-Deficient Recombinant Adenovirus Serotype 5 Vaccine Expressing Guanylate Cyclase C and the PADRE T-helper Epitope.Human gene therapy methods · 2016Article
- Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials.Scientific reports · 2016Article
- Preclinical Efficacy and Safety Profile of Allometrically Scaled Doses of Doxycycline Used to Turn "On" Therapeutic Transgene Expression from High-Capacity Adenoviral Vectors in a Glioma Model.Human gene therapy methods · 2016Article
- Reprogramming the conduction system: Onward toward a biological pacemaker.Trends in cardiovascular medicine · 2016Review
- Overview of current immunotherapeutic strategies for glioma.Immunotherapy · 2015Review
- Adenoviral vector-mediated gene therapy for gliomas: coming of age.Expert opinion on biological therapy · 2014Review
- Feasibility of Applying Helper-Dependent Adenoviral Vectors for Cancer Immunotherapy.Biomedicines · 2014Review
- Development of preclinical models for immunogene therapy of brain cancer: it's not monkey business!Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Safety profile, efficacy, and biodistribution of a bicistronic high-capacity adenovirus vector encoding a combined immunostimulation and cytotoxic gene therapy as a prelude to a phase I clinical trial for glioblastoma.Toxicology and applied pharmacology · 2013Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Glioblastoma multiforme (GBM) is a deadly primary brain tumor. Conditional cytotoxic/immune-stimulatory gene therapy (Ad-TK and Ad-Flt3L) elicits tumor regression and immunological memory in rodent GBM models. Since the majority of patients enrolled in clinical trials would exhibit adenovirus immunity, which could curtail transgene expression and therapeutic efficacy, we used high-capacity adenovirus vectors (HC-Ads) as a gene delivery platform. Herein, we describe for the first time a novel bicistronic HC-Ad driving constitutive expression of herpes simplex virus type 1 thymidine kinase (HSV1-TK) and inducible Tet-mediated expression of Flt3L within a single-vector platform. We achieved anti-GBM therapeutic efficacy with no overt toxicities using this bicistronic HC-Ad even in the presence of systemic Ad immunity. The bicistronic HC-Ad-TK/TetOn-Flt3L was delivered into intracranial gliomas in rats. Survival, vector biodistribution, neuropathology, systemic toxicity, and neurobehavioral deficits were assessed for up to 1 year posttreatment. Therapeutic efficacy was also assessed in animals preimmunized against Ads. We demonstrate therapeutic efficacy, with vector genomes being restricted to the brain injection site and an absence of overt toxicities. Importantly, antiadenoviral immunity did not inhibit therapeutic efficacy. These data represent the first report of a bicistronic vector platform driving the expression of two therapeutic transgenes, i.e., constitutive HSV1-TK and inducible Flt3L genes. Further, our data demonstrate no promoter interference and optimum gene delivery and expression from within this single-vector platform. Analysis of the efficacy, safety, and toxicity of this bicistronic HC-Ad vector in an animal model of GBM strongly supports further preclinical testing and downstream process development of HC-Ad-TK/TetOn-Flt3L for a future phase I clinical trial for GBM.
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Registered trials
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.