ArticleGene therapy2015
γ₁34.5-deleted HSV-1-expressing human cytomegalovirus IRS1 gene kills human glioblastoma cells as efficiently as wild-type HSV-1 in normoxia or hypoxia.
Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 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
25 citing papers in PubMed, 29 citations in OpenAlex.
- Oncolytic Herpes Simplex Virus Therapy: Latest Advances, Core Challenges, and Future Outlook.Vaccines · 2025Review
- Advances in the Drug Development and Quality Evaluation Principles of Oncolytic Herpes Simplex Virus.Viruses · 2025Review
- Oncolytic herpes simplex viruses for the treatment of glioma and targeting glioblastoma stem-like cells.Frontiers in cellular and infection microbiology · 2023Review
- Review
- Multiple strategies to improve the therapeutic efficacy of oncolytic herpes simplex virus in the treatment of glioblastoma.Oncology letters · 2021Review
- Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas.Neurosurgery clinics of North America · 2021Review
- Antitumor effects of IL-12 and GM-CSF co-expressed in an engineered oncolytic HSV-1.Gene therapy · 2021Article
- The Association of Human Herpesviruses with Malignant Brain Tumor Pathology and Therapy: Two Sides of a Coin.International journal of molecular sciences · 2021Review
- Clinically Explored Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma in Adults.Biomedicines · 2021Review
- The Current State of Oncolytic Herpes Simplex Virus for Glioblastoma Treatment.Oncolytic virotherapy · 2021Review
- Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy.Molecular cancer · 2020Review
- Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy.International journal of molecular sciences · 2020Review
- Herpes Simplex Virus 1 ICP34.5 Alters Mitochondrial Dynamics in Neurons.Journal of virology · 2020Article
- Tumor Control by Cytomegalovirus: A Door Open for Oncolytic Virotherapy?Molecular therapy oncolytics · 2020Review
- Preclinical Toxicology of rQNestin34.5v.2: An Oncolytic Herpes Virus with Transcriptional Regulation of the ICP34.5 Neurovirulence Gene.Molecular therapy. Methods & clinical development · 2020Article
- Review
- Biocompatibility of common implantable sensor materials in a tumor xenograft model.Journal of biomedical materials research. Part B, Applied biomaterials · 2019Article
- Chimeric HCMV/HSV-1 and ΔγTranslational oncology · 2018Article
- Addressing the Adult Soft Tissue Sarcoma Microenvironment with Intratumoral Immunotherapy.Sarcoma · 2018Review
- Role of Herpes Simplex Virus 1 γ34.5 in the Regulation of IRF3 Signaling.Journal of virology · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Pathophysiological hypoxia, which fosters the glioma stem-like cell (GSC) phenotype, is present in high-grade gliomas and has been linked to tumor development, invasiveness and resistance to chemotherapy and radiation. Oncolytic virotherapy with engineered herpes simplex virus-1 (HSV-1) is a promising therapy for glioblastoma; however, the efficacy of γ(1)34.5-deleted HSVs, which have been used in clinical trials, was diminished in hypoxia. We investigated the ability of a chimeric human cytolomegalovirus (HCMV)/HSV-1 virus, which expresses the human CMV protein kinase R evasion gene IRS1 and is in preparation for clinical trials, to infect and kill adult and pediatric patient-derived glioblastoma xenografts in hypoxia and normoxia. Infectivity, cytotoxicity and viral recovery were significantly greater with the chimeric virus compared with the γ(1)34.5-deleted virus, regardless of oxygen tension. The chimeric virus infected and killed CD133+ GSCs similarly to wild-type HSV-1. Increased activation of mitogen-activated protein kinase p38 and its substrate heat-shock protein 27 (Hsp27) was seen after viral infection in normoxia compared with hypoxia. Hsp27 knockdown or p38 inhibition reduced virus recovery, indicating that the p38 pathway has a role in the reduced efficacy of the γ(1)34.5-deleted virus in hypoxia. Taken together, these findings demonstrate that chimeric HCMV/HSV-1 efficiently targets both CD133+ GSCs and glioma cells in hypoxia.
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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.