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.

Virology
|July 29, 2018
PubMed

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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