ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Safety and Efficacy of Intraventricular Immunovirotherapy with Oncolytic HSV-1 for CNS Cancers.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Antitumor activity of Oncolytic Herpes Symplex Virus Type 1 and photodynamic therapy in in vitro preclinical models of glioblastoma.Journal of translational medicine · 2026Article
- Oncolytic viruses and cytokine-based gene therapies reprogram the tumor microenvironment.Nature cancer · 2026Review
- Neural stem cell-delivered oncolytic virus via intracerebroventricular administration enhances glioblastoma therapy and immune modulation.Journal for immunotherapy of cancer · 2025Article
- Translational advancements in tumor vaccine therapies for glioblastomas.Neuro-oncology advances · 2025Review
- Challenges and strategies toward oncolytic virotherapy for leptomeningeal metastasis.Journal of translational medicine · 2024Review
- Safety of non-replicative and oncolytic replication-selective HSV vectors.Trends in molecular medicine · 2024Review
- Recurrent Glioblastoma-Molecular Underpinnings and Evolving Treatment Paradigms.International journal of molecular sciences · 2024Review
- The safety and accuracy of intratumoral catheter placement to infuse viral immunotherapies in children with malignant brain tumors: a multi-institutional study.Journal of neurosurgery. Pediatrics · 2024Article
- Oncolytic Virotherapy for High-Grade Glioma and Current Evidence and Factors to Consider for Incorporation into Clinical Practice.Pathogens (Basel, Switzerland) · 2023Review
- Intraventricular immunovirotherapy; a translational step forward.Oncotarget · 2023Article
- Recent oncolytic virotherapy clinical trials outline a roadmap for the treatment of high-grade glioma.Neuro-oncology advancesReview
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
purposeOncolytic virotherapy with herpes simplex virus-1 (HSV) has shown promise for the treatment of pediatric and adult brain tumors; however, completed and ongoing clinical trials have utilized intratumoral/peritumoral oncolytic HSV (oHSV) inoculation due to intraventricular/intrathecal toxicity concerns. Intratumoral delivery requires an invasive neurosurgical procedure, limits repeat injections, and precludes direct targeting of metastatic and leptomeningeal disease. To address these limitations, we determined causes of toxicity from intraventricular oHSV and established methods for mitigating toxicity to treat disseminated brain tumors in mice. EXPERIMENTAL
designHSV-sensitive CBA/J mice received intraventricular vehicle, inactivated oHSV, or treatment doses (1×107 plaque-forming units) of oHSV, and toxicity was assessed by weight loss and IHC. Protective strategies to reduce oHSV toxicity, including intraventricular low-dose oHSV or interferon inducer polyinosinic-polycytidylic acid (poly I:C) prior to oHSV treatment dose, were evaluated and then utilized to assess intraventricular oHSV treatment of multiple models of disseminated CNS disease.
resultsA standard treatment dose of intraventricular oHSV damaged ependymal cells via virus replication and induction of CD8+ T cells, whereas vehicle or inactivated virus resulted in no toxicity. Subsequent doses of intraventricular oHSV caused little additional toxicity. Interferon induction with phosphorylation of eukaryotic initiation factor-2α (eIF2α) via intraventricular pretreatment with low-dose oHSV or poly I:C mitigated ependyma toxicity. This approach enabled the safe delivery of multiple treatment doses of clinically relevant oHSV G207 and prolonged survival in disseminated brain tumor models.
conclusionsToxicity from intraventricular oHSV can be mitigated, resulting in therapeutic benefit. These data support the clinical translation of intraventricular G207.
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Registered trials
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