Intravenously administered alphavirus vector VA7 eradicates orthotopic human glioma xenografts in nude mice.

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...

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Main Authors: Jari E Heikkilä, Markus J V Vähä-Koskela, Janne J Ruotsalainen, Miika W Martikainen, Marianne M Stanford, J Andrea McCart, John C Bell, Ari E Hinkkanen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2799335?pdf=render
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spelling doaj-9e3d7804e4a04a5ba6d78d9f1539f1472020-11-24T20:51:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0151e860310.1371/journal.pone.0008603Intravenously administered alphavirus vector VA7 eradicates orthotopic human glioma xenografts in nude mice.Jari E HeikkiläMarkus J V Vähä-KoskelaJanne J RuotsalainenMiika W MartikainenMarianne M StanfordJ Andrea McCartJohn C BellAri E HinkkanenVA7 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.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.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.http://europepmc.org/articles/PMC2799335?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Jari E Heikkilä
Markus J V Vähä-Koskela
Janne J Ruotsalainen
Miika W Martikainen
Marianne M Stanford
J Andrea McCart
John C Bell
Ari E Hinkkanen
spellingShingle Jari E Heikkilä
Markus J V Vähä-Koskela
Janne J Ruotsalainen
Miika W Martikainen
Marianne M Stanford
J Andrea McCart
John C Bell
Ari E Hinkkanen
Intravenously administered alphavirus vector VA7 eradicates orthotopic human glioma xenografts in nude mice.
PLoS ONE
author_facet Jari E Heikkilä
Markus J V Vähä-Koskela
Janne J Ruotsalainen
Miika W Martikainen
Marianne M Stanford
J Andrea McCart
John C Bell
Ari E Hinkkanen
author_sort Jari E Heikkilä
title Intravenously administered alphavirus vector VA7 eradicates orthotopic human glioma xenografts in nude mice.
title_short Intravenously administered alphavirus vector VA7 eradicates orthotopic human glioma xenografts in nude mice.
title_full Intravenously administered alphavirus vector VA7 eradicates orthotopic human glioma xenografts in nude mice.
title_fullStr Intravenously administered alphavirus vector VA7 eradicates orthotopic human glioma xenografts in nude mice.
title_full_unstemmed Intravenously administered alphavirus vector VA7 eradicates orthotopic human glioma xenografts in nude mice.
title_sort intravenously administered alphavirus vector va7 eradicates orthotopic human glioma xenografts in nude mice.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2010-01-01
description 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.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.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.
url http://europepmc.org/articles/PMC2799335?pdf=render
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