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Updated: Feb 7, 2026

A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies
Published on: November 7, 2015
Chikungunya-vesicular stomatitis chimeric virus targets and eliminates brain tumors
Xue Zhang1, Guochao Mao1, Anthony N van den Pol1
1Department of Neurosurgery, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520, United States.
Abstract:
Vesicular stomatitis virus (VSV) shows potential for targeting and killing cancer cells, but can be dangerous in the brain due to its neurotropic glycoprotein. Here we test a chimeric virus in which the VSV glycoprotein is replaced with the Chikungunya polyprotein E3-E2-6K-E1 (VSVΔG-CHIKV). Control mice with brain tumors survived a mean of 40 days after tumor implant. VSVΔG-CHIKV selectively infected and eliminated the tumor, and extended survival substantially in all tumor-bearing mice to over 100 days. VSVΔG-CHIKV also targeted intracranial primary patient derived melanoma xenografts. Virus injected into one melanoma spread to other melanomas within the same brain with little detectable infection of normal cells. Intravenous VSVΔG-CHIKV infected tumor cells but not normal tissue. In immunocompetent mice, VSVΔG-CHIKV selectively infected mouse melanoma cells within the brain. These data suggest VSVΔG-CHIKV can target and destroy brain tumors in multiple animal models without the neurotropism associated with the wild type VSV glycoprotein.
Insights
A modified vesicular stomatitis virus (VSV), VSVΔG-CHIKV, effectively targets and eliminates brain tumors in mice. This engineered virus shows promise for treating brain cancers without the dangerous neurotropic effects of wild-type VSV.
Area of Science:
- Oncolytic virotherapy
- Viral oncology
- Neuro-oncology
Background:
- Vesicular stomatitis virus (VSV) demonstrates potential for cancer cell targeting and destruction.
- Wild-type VSV's neurotropic glycoprotein poses significant risks for brain applications.
- Chimeric viruses offer a strategy to modify viral tropism and safety profiles.
Purpose of the Study:
- To evaluate the efficacy and safety of a chimeric VSV, VSVΔG-CHIKV, engineered with a Chikungunya virus glycoprotein.
- To determine if VSVΔG-CHIKV can effectively target and eliminate brain tumors, including melanoma xenografts.
- To assess the virus's infectivity in normal brain tissue and its behavior after systemic administration.
Main Methods:
- Construction of a chimeric virus, VSVΔG-CHIKV, replacing the VSV glycoprotein with Chikungunya virus polyprotein.
- Administration of VSVΔG-CHIKV to mice with intracranial brain tumors and melanoma xenografts.
- Evaluation of tumor targeting, viral spread, survival rates, and infection of normal tissues in various mouse models.
Main Results:
- VSVΔG-CHIKV significantly extended survival in mice with brain tumors, from a mean of 40 days to over 100 days.
- The chimeric virus selectively infected and eliminated both established brain tumors and patient-derived melanoma xenografts.
- Intravenous administration of VSVΔG-CHIKV demonstrated tumor cell targeting with minimal infection of normal tissues.
- The virus effectively targeted and infected mouse melanoma cells within the brain of immunocompetent mice.
Conclusions:
- VSVΔG-CHIKV represents a promising oncolytic virus for brain tumor therapy, mitigating the neurotropism associated with wild-type VSV.
- The engineered virus demonstrates broad targeting capabilities for intracranial tumors, including melanoma, via direct injection and systemic delivery.
- VSVΔG-CHIKV shows potential for safe and effective treatment of brain malignancies in preclinical models.
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