ArticleHuman gene therapy. Clinical development2014
Evaluation of the safety and biodistribution of M032, an attenuated herpes simplex virus type 1 expressing hIL-12, after intracerebral administration to aotus nonhuman primates.
Article in Human gene therapy. Clinical development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 74 citations in OpenAlex.
- Triple-Survival Stereotactic Brain Surgeries for the Intracranial Injections of Glioblastoma Stem-like Cells and Oncolytic Herpes Simplex Viruses.Methods and protocols · 2026Article
- Oncolytic Herpes Simplex Virus for Glioblastoma: Molecular Engineering, Tumor Microenvironment Barriers, and Clinical Translation.Current issues in molecular biology · 2026Review
- Intracranial injection of genetically modified, mosquito non-transmissible Zika virus: Safety in primates and ramifications for brain tumor therapy.Cell reports. Medicine · 2025Article
- Oncolytic HSV and cancer drug interactions: Current clinical status and future directions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- An oncolytic herpes simplex virus armed with IL-12 for treatment of preclinical glioblastoma.Molecular therapy. Oncology · 2025Article
- Oncolytic Herpes Simplex Virus Therapy: Latest Advances, Core Challenges, and Future Outlook.Vaccines · 2025Review
- Modeling Virus-Associated Central Nervous System Disease in Non-Human Primates.International journal of molecular sciences · 2025Review
- Oncolytic HSV-IL27 expression improves CD8 T cell function and therapeutic activity in syngeneic glioma models.Journal for immunotherapy of cancer · 2025Article
- Oncolytic reprogramming of tumor microenvironment shapes CD4 T-cell memory via the IL6ra-Bcl6 axis for targeted control of glioblastoma.Nature communications · 2025Article
- Comparative oncology in action: vignettes on immunotherapy development.Veterinary oncology (London, England) · 2025Review
- Oncolytic Virotherapies and Adjuvant Gut Microbiome Therapeutics to Enhance Efficacy Against Malignant Gliomas.Viruses · 2024Review
- Safety of non-replicative and oncolytic replication-selective HSV vectors.Trends in molecular medicine · 2024Review
- Review
- A viral attack on brain tumors: the potential of oncolytic virus therapy.Journal of neurovirology · 2024Review
- Cytokine-armed oncolytic herpes simplex viruses: a game-changer in cancer immunotherapy?Journal for immunotherapy of cancer · 2024Review
- Combination of Oncolytic Virotherapy with Different Antitumor Approaches against Glioblastoma.International journal of molecular sciences · 2024Review
- Enhanced IL-12 transgene expression improves oncolytic viroimmunotherapy.Frontiers in immunology · 2024Article
- Novel Therapies in Glioblastoma Treatment: Review of Glioblastoma; Current Treatment Options; and Novel Oncolytic Viral Therapies.Medical sciences (Basel, Switzerland) · 2023Review
- Review
- Current Status and Challenges of Oncolytic Virotherapy for the Treatment of Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2023Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Herpes simplex virus type 1 (HSV-1) mutants lacking the γ(1)34.5 neurovirulence loci are promising agents for treating malignant glioma. Arming oncolytic HSV-1 to express immunostimulatory genes may potentiate therapeutic efficacy. We have previously demonstrated improved preclinical efficacy, biodistribution, and safety of M002, a γ(1)34.5-deleted HSV-1 engineered to express murine IL-12. Herein, we describe the safety and biodistribution of M032, a γ(1)34.5-deleted HSV-1 virus that expresses human IL-12 after intracerebral administration to nonhuman primates, Aotus nancymae. Cohorts were administered vehicle, 10(6), or 10(8) pfu of M032 on day 1 and subjected to detailed clinical observations performed serially over a 92-day trial. Animals were sacrificed on days 3, 31, and 91 for detailed histopathologic assessments of all organs and to isolate and quantify virus in all organs. With the possible exception of one animal euthanized on day 16, neither adverse clinical signs nor sex- or dose-related differences were attributed to M032. Elevated white blood cell and neutrophil counts were observed in virus-injected groups on day 3, but no other significant changes were noted in clinical chemistry or coagulation parameters. Minimal to mild inflammation and fibrosis detected, primarily in meningeal tissues, in M032-injected animals on days 3 and 31 had mostly resolved by day 91. The highest viral DNA levels were detected at the injection site and motor cortex on day 3 but decreased in central nervous system tissues over time. These data demonstrate the requisite safety of intracerebral M032 administration for consideration as a therapeutic for treating malignant brain tumors.
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