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Updated: Jun 19, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Enhanced antitumor efficacy of vasculostatin (Vstat120) expressing oncolytic HSV-1
Jayson Hardcastle1, Kazuhiko Kurozumi, Nina Dmitrieva
1Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, James Comprehensive Cancer Center and The Ohio State University Medical Center, Columbus, Ohio 43210, USA.
Abstract:
Oncolytic viral (OV) therapy is a promising therapeutic modality for brain tumors. Vasculostatin (Vstat120) is the cleaved and secreted extracellular fragment of brain-specific angiogenesis inhibitor 1 (BAI1), a brain-specific receptor. To date, the therapeutic efficacy of Vstat120 delivery into established tumors has not been investigated. Here we tested the therapeutic efficacy of combining Vstat120 gene delivery in conjunction with OV therapy. We constructed RAMBO (Rapid Antiangiogenesis Mediated By Oncolytic virus), which expresses Vstat120 under the control of the herpes simplex virus (HSV) IE4/5 promoter. Secreted Vstat120 was detected as soon as 4 hours postinfection in vitro and was retained for up to 13 days after OV therapy in subcutaneous tumors. RAMBO-produced Vstat120 efficiently inhibited endothelial cell migration and tube formation in vitro (P = 0.0005 and P = 0.0184, respectively) and inhibited angiogenesis (P = 0.007) in vivo. There was a significant suppression of intracranial and subcutaneous glioma growth in mice treated with RAMBO compared to the control virus, HSVQ (P = 0.0021 and P < 0.05, respectively). Statistically significant reduction in tumor vascular volume fraction (VVF) and microvessel density (MVD) was observed in tumors treated with RAMBO. This is the first study to report the antitumor effects of Vstat120 delivery into established tumors and supports the further development of RAMBO as a possible cancer therapy.
Insights
This study introduces RAMBO, a novel oncolytic virus therapy combining Vasculostatin (Vstat120) gene delivery with viral therapy. RAMBO effectively inhibits tumor growth and angiogenesis in brain tumors, showing promise for cancer treatment.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Oncolytic viral (OV) therapy shows potential for brain tumor treatment.
- Vasculostatin (Vstat120) is a fragment of BAI1 that inhibits angiogenesis.
- The efficacy of Vstat120 delivery into established tumors remains uninvestigated.
Purpose of the Study:
- To investigate the therapeutic efficacy of combining Vstat120 gene delivery with OV therapy.
- To construct and evaluate a novel oncolytic virus, RAMBO, expressing Vstat120.
Main Methods:
- Constructed RAMBO (Rapid Antiangiogenesis Mediated By Oncolytic virus) expressing Vstat120.
- Assessed Vstat120 secretion in vitro and in vivo.
- Evaluated inhibition of endothelial cell migration, tube formation, and angiogenesis.
- Tested RAMBO efficacy in intracranial and subcutaneous glioma models in mice.
Main Results:
- RAMBO-produced Vstat120 was secreted rapidly and persisted in tumors.
- Vstat120 significantly inhibited endothelial cell functions and angiogenesis in vitro and in vivo.
- RAMBO significantly suppressed glioma growth in both intracranial and subcutaneous models.
- RAMBO treatment led to reduced tumor vascular volume fraction and microvessel density.
Conclusions:
- This study is the first to demonstrate antitumor effects of Vstat120 delivery into established tumors.
- RAMBO shows significant potential as a novel cancer therapy by combining OV and anti-angiogenic strategies.
- Further development of RAMBO is supported for potential clinical application in cancer treatment.
