ArticleScientific reports2018
A hypoxia- and telomerase-responsive oncolytic adenovirus expressing secretable trimeric TRAIL triggers tumour-specific apoptosis and promotes viral dispersion in TRAIL-resistant glioblastoma.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 50 citations in OpenAlex.
- Reassessing Viral Gene Therapy for Glioblastoma: Translational Opportunities and Challenges.The Yale journal of biology and medicine · 2026Article
- Oncolytic adenovirus in combination with PD-L1-targeted radioimmunotherapy exerts synergistic antitumor effect against pancreatic cancer.Journal for immunotherapy of cancer · 2026Article
- Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).International journal of molecular medicine · 2025Review
- Combination therapies and novel delivery systems: a new frontier in overcoming TRAIL resistance in gastric cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Review
- A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.Cancers · 2025Review
- Artificial intelligence analysis applied to the treatment of granulosa cell tumors of the ovary.Frontiers in artificial intelligence · 2025Article
- Beginning at the ends: telomere and telomere-based cancer therapeutics.Molecular genetics and genomics : MGG · 2024Review
- Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy.Nature protocols · 2024Review
- An Update on the Clinical Status, Challenges, and Future Directions of Oncolytic Virotherapy for Malignant Gliomas.Current treatment options in oncology · 2024Review
- Oncolytic Virotherapy: A New Paradigm in Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- Tumor microenvironment-modulating oncolytic adenovirus combined with GSK-3β inhibitor enhances antitumor immune response against bladder cancer.Frontiers in immunology · 2024Article
- Mathematical modeling predicts pathways to successful implementation of combination TRAIL-producing oncolytic virus and PAC-1 to treat granulosa cell tumors of the ovary.Cancer biology & therapy · 2023Article
- Anticancer Activity of Measles-Mumps-Rubella MMR Vaccine Viruses against Glioblastoma.Cancers · 2023Article
- Oncolytic virotherapy: basic principles, recent advances and future directions.Signal transduction and targeted therapy · 2023Review
- Myeloidcells in the immunosuppressive microenvironment in glioblastoma: The characteristics and therapeutic strategies.Frontiers in immunology · 2023Review
- Oncolytic viruses-modulated immunogenic cell death, apoptosis and autophagy linking to virotherapy and cancer immune response.Frontiers in cellular and infection microbiology · 2023Review
- Modifying oncolytic virotherapy to overcome the barrier of the hypoxic tumor microenvironment. Where do we stand?Cancer cell international · 2022Review
- ErbB3-Targeting Oncolytic Adenovirus Causes Potent Tumor Suppression by Induction of Apoptosis in Cancer Cells.International journal of molecular sciences · 2022Article
- Agent-based computational modeling of glioblastoma predicts that stromal density is central to oncolytic virus efficacy.iScience · 2022Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma is a highly aggressive and malignant type of cancer that is apoptosis resistant and difficult to cure by conventional cancer therapies. In this regard, an oncolytic adenovirus that selectively targets the tumour tissue and induces tumour cell lysis is a promising treatment option. We designed and constructed a hypoxia-responsive and cancer-specific modified human telomerase reverse transcriptase (H5CmTERT) promoter to drive replication of an oncolytic adenovirus (H5CmTERT-Ad). To enhance the anti-tumour efficacy of H5CmTERT-Ad against malignant glioblastoma, we also generated an H5CmTERT-Ad expressing secretable trimeric tumour necrosis factor-related apoptosis-inducing ligand (H5CmTERT-Ad/TRAIL). H5CmTERT promoter-regulated oncolytic adenoviruses showed cancer-specific and superior cell-killing effect in contrast to a cognate control oncolytic adenovirus replicating under the control of the endogenous adenovirus promoter. The cancer cell-killing effects of H5CmTERT-Ad and H5CmTERT-Ad/TRAIL were markedly higher during hypoxia than normoxia owing to hypoxia responsiveness of the promoter. H5CmTERT-Ad/TRAIL showed more potent anti-tumour efficacy than H5CmTERT-Ad did in a xenograft model of TRAIL-resistant subcutaneous and orthotopic glioblastoma through superior induction of apoptosis and more extensive virus distribution in the tumour tissue. Altogether, our findings show that H5CmTERT-Ad/TRAIL can promote dispersion of an oncolytic adenovirus through robust induction of apoptosis in a highly TRAIL-resistant glioblastoma.
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