Pseudotyping vesicular stomatitis virus with lymphocytic choriomeningitis virus glycoproteins enhances infectivity for glioma cells and minimizes neurotropism |
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| Authors: | Muik Alexander Kneiske Inna Werbizki Marina Wilflingseder Doris Giroglou Tsanan Ebert Oliver Kraft Anna Dietrich Ursula Zimmer Gert Momma Stefan von Laer Dorothee |
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| Affiliation: | 1Georg-Speyer-Haus, Frankfurt am Main, Germany;2Division of Virology, Innsbruck Medical University, Innsbruck, Austria;3Medizinische Klinik und Poliklinik II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany;4Institute of Neurology (Edinger Institute), University of Frankfurt, Frankfurt am Main, Germany;5Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland |
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| Abstract: | Vesicular stomatitis virus (VSV)-based oncolytic virotherapy has the potential to significantly improve the prognosis of aggressive malignancies such as brain cancer. However, VSV's inherent neurotoxicity has hindered clinical development so far. Given that this neurotropism is attributed to the glycoprotein VSV-G, VSV was pseudotyped with the nonneurotropic envelope glycoprotein of the lymphocytic choriomeningitis virus (LCMV-GP→VSV-GP). Compared to VSV, VSV-GP showed enhanced infectivity for brain cancer cells in vitro while sparing primary human and rat neurons in vitro and in vivo, respectively. In conclusion, VSV-GP has a much wider therapeutic window than VSV and is thus more suitable for clinical applications, especially in the brain. |
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