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Updated: Jun 17, 2026
Creating Anatomically Accurate and Reproducible Intracranial Xenografts of Human Brain Tumors
Published on: September 24, 2014
Intravenously administered alphavirus vector VA7 eradicates orthotopic human glioma xenografts in nude mice
Jari E Heikkilä1, Markus J V Vähä-Koskela, Janne J Ruotsalainen
1Department of Biochemistry and Pharmacy, Abo Akademi University, Turku, Finland. jari.heikkila@abo.fi
Background:
VA7 is a neurotropic alphavirus vector based on an attenuated strain of Semliki Forest virus. We have previously shown that VA7 exhibits oncolytic activity against human melanoma xenografts in immunodeficient mice. The purpose of this study was to determine if intravenously administered VA7 would be effective against human glioma.
Methodology/Principal Findings:
In vitro, U87, U251, and A172 human glioma cells were infected and killed by VA7-EGFP. In vivo, antiglioma activity of VA7 was tested in Balb/c nude mice using U87 cells stably expressing firefly luciferase in subcutaneous and orthotopic tumor models. Intravenously administered VA7-EGFP completely eradicated 100% of small and 50% of large subcutaneous U87Fluc tumors. A single intravenous injection of either VA7-EGFP or VA7 expressing Renilla luciferase (VA7-Rluc) into mice bearing orthotopic U87Fluc tumors caused a complete quenching of intracranial firefly bioluminescence and long-term survival in total 16 of 17 animals. In tumor-bearing mice injected with VA7-Rluc, transient intracranial and peripheral Renilla bioluminescence was observed. Virus was well tolerated and no damage to heart, liver, spleen, or brain was observed upon pathological assessment at three and ninety days post injection, despite detectable virus titers in these organs during the earlier time point.
Conclusion:
VA7 vector is apathogenic and can enter and destroy brain tumors in nude mice when administered systemically. This study warrants further elucidation of the mechanism of tumor destruction and attenuation of the VA7 virus.
Insights
The VA7 alphavirus vector effectively targets and destroys human glioma cells in mice after intravenous administration. This neurotropic vector shows promise for treating brain tumors with no observed toxicity.
Area of Science:
- Virology
- Oncology
- Gene Therapy
Background:
- VA7 is a neurotropic alphavirus vector derived from Semliki Forest virus.
- Previous studies demonstrated VA7's oncolytic activity against melanoma xenografts in immunodeficient mice.
Purpose of the Study:
- To evaluate the efficacy of systemically administered VA7 against human glioma in vivo.
Main Methods:
- In vitro infection and killing of human glioma cell lines (U87, U251, A172) by VA7-EGFP.
- In vivo studies in Balb/c nude mice using subcutaneous and orthotopic U87Fluc glioma models.
- Assessment of antiglioma activity and toxicity following intravenous VA7 administration.
Main Results:
- VA7-EGFP eradicated 100% of small and 50% of large subcutaneous U87Fluc tumors.
- A single intravenous injection of VA7 led to complete tumor bioluminescence quenching and long-term survival in 16 of 17 mice with orthotopic tumors.
- Pathological assessment revealed no significant organ damage, indicating good tolerability despite detectable viral titers.
Conclusions:
- The VA7 vector is apathogenic and effectively enters and destroys brain tumors in mice upon systemic administration.
- Further research is warranted to understand the tumor destruction mechanisms and optimize VA7 attenuation.
