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Specificity, Safety, Efficacy of EGFRvIII-Retargeted Oncolytic HSV for Xenotransplanted Human Glioblastoma

Glioblastoma is a lethal primary brain tumor lacking effective therapy. The secluded onset site, combined with the infiltrative properties of this tumor, require novel targeted therapies. In this scenario, the use of oncolytic viruses retargeted to glioblastoma cells and able to spread across the tu...

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Autores principales: Appolloni, Irene, Alessandrini, Francesco, Menotti, Laura, Avitabile, Elisa, Marubbi, Daniela, Piga, Noemi, Ceresa, Davide, Piaggio, Francesca, Campadelli-Fiume, Gabriella, Malatesta, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473268/
https://www.ncbi.nlm.nih.gov/pubmed/34578259
http://dx.doi.org/10.3390/v13091677
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author Appolloni, Irene
Alessandrini, Francesco
Menotti, Laura
Avitabile, Elisa
Marubbi, Daniela
Piga, Noemi
Ceresa, Davide
Piaggio, Francesca
Campadelli-Fiume, Gabriella
Malatesta, Paolo
author_facet Appolloni, Irene
Alessandrini, Francesco
Menotti, Laura
Avitabile, Elisa
Marubbi, Daniela
Piga, Noemi
Ceresa, Davide
Piaggio, Francesca
Campadelli-Fiume, Gabriella
Malatesta, Paolo
author_sort Appolloni, Irene
collection PubMed
description Glioblastoma is a lethal primary brain tumor lacking effective therapy. The secluded onset site, combined with the infiltrative properties of this tumor, require novel targeted therapies. In this scenario, the use of oncolytic viruses retargeted to glioblastoma cells and able to spread across the tumor cells represent an intriguing treatment strategy. Here, we tested the specificity, safety and efficacy of R-613, the first oncolytic HSV fully retargeted to EGFRvIII, a variant of the epidermal growth factor receptor carrying a mutation typically found in glioblastoma. An early treatment with R-613 on orthotopically transplanted EGFRvIII-expressing human glioblastoma significantly increased the median survival time of mice. In this setting, the growth of human glioblastoma xenotransplants was monitored by a secreted luciferase reporter and showed that R-613 is able to substantially delay the development of the tumor masses. When administered as late treatment to a well-established glioblastomas, R-613 appeared to be less effective. Notably the uninfected tumor cells derived from the explanted tumor masses were still susceptible to R-613 infection ex vivo, thus suggesting that multiple treatments could enhance R-613 therapeutic efficacy, making R-613 a promising oncolytic HSV candidate for glioblastoma treatment.
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spelling pubmed-84732682021-09-28 Specificity, Safety, Efficacy of EGFRvIII-Retargeted Oncolytic HSV for Xenotransplanted Human Glioblastoma Appolloni, Irene Alessandrini, Francesco Menotti, Laura Avitabile, Elisa Marubbi, Daniela Piga, Noemi Ceresa, Davide Piaggio, Francesca Campadelli-Fiume, Gabriella Malatesta, Paolo Viruses Article Glioblastoma is a lethal primary brain tumor lacking effective therapy. The secluded onset site, combined with the infiltrative properties of this tumor, require novel targeted therapies. In this scenario, the use of oncolytic viruses retargeted to glioblastoma cells and able to spread across the tumor cells represent an intriguing treatment strategy. Here, we tested the specificity, safety and efficacy of R-613, the first oncolytic HSV fully retargeted to EGFRvIII, a variant of the epidermal growth factor receptor carrying a mutation typically found in glioblastoma. An early treatment with R-613 on orthotopically transplanted EGFRvIII-expressing human glioblastoma significantly increased the median survival time of mice. In this setting, the growth of human glioblastoma xenotransplants was monitored by a secreted luciferase reporter and showed that R-613 is able to substantially delay the development of the tumor masses. When administered as late treatment to a well-established glioblastomas, R-613 appeared to be less effective. Notably the uninfected tumor cells derived from the explanted tumor masses were still susceptible to R-613 infection ex vivo, thus suggesting that multiple treatments could enhance R-613 therapeutic efficacy, making R-613 a promising oncolytic HSV candidate for glioblastoma treatment. MDPI 2021-08-24 /pmc/articles/PMC8473268/ /pubmed/34578259 http://dx.doi.org/10.3390/v13091677 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Appolloni, Irene
Alessandrini, Francesco
Menotti, Laura
Avitabile, Elisa
Marubbi, Daniela
Piga, Noemi
Ceresa, Davide
Piaggio, Francesca
Campadelli-Fiume, Gabriella
Malatesta, Paolo
Specificity, Safety, Efficacy of EGFRvIII-Retargeted Oncolytic HSV for Xenotransplanted Human Glioblastoma
title Specificity, Safety, Efficacy of EGFRvIII-Retargeted Oncolytic HSV for Xenotransplanted Human Glioblastoma
title_full Specificity, Safety, Efficacy of EGFRvIII-Retargeted Oncolytic HSV for Xenotransplanted Human Glioblastoma
title_fullStr Specificity, Safety, Efficacy of EGFRvIII-Retargeted Oncolytic HSV for Xenotransplanted Human Glioblastoma
title_full_unstemmed Specificity, Safety, Efficacy of EGFRvIII-Retargeted Oncolytic HSV for Xenotransplanted Human Glioblastoma
title_short Specificity, Safety, Efficacy of EGFRvIII-Retargeted Oncolytic HSV for Xenotransplanted Human Glioblastoma
title_sort specificity, safety, efficacy of egfrviii-retargeted oncolytic hsv for xenotransplanted human glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473268/
https://www.ncbi.nlm.nih.gov/pubmed/34578259
http://dx.doi.org/10.3390/v13091677
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