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COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA
BACKGROUND: High-grade gliomas (HGG) pose therapeutic challenges stemming from blood brain barrier, infiltrative growth, suppressed immune function, and tumor heterogeneity. Oncolytic viruses (OVs) are gaining traction for addressing these challenges. There is evidence that the SARS-CoV-2 glycoprote...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650446/ http://dx.doi.org/10.1093/neuonc/noaa215.101 |
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author | Immidisetti, Amanda Munier, Sean Patel, Nitesh |
author_facet | Immidisetti, Amanda Munier, Sean Patel, Nitesh |
author_sort | Immidisetti, Amanda |
collection | PubMed |
description | BACKGROUND: High-grade gliomas (HGG) pose therapeutic challenges stemming from blood brain barrier, infiltrative growth, suppressed immune function, and tumor heterogeneity. Oncolytic viruses (OVs) are gaining traction for addressing these challenges. There is evidence that the SARS-CoV-2 glycoprotein spike binds the ACE-2 receptor in nasal epithelium and reaches the brainstem and thalamus via axonal transport through the olfactory pathway, making it an attractive candidate for OV therapy. Prior studies on chimerization of pathogenic virus-derived glycoprotein spikes with non-pathogenic strains exploit neurotropism of a wild-type virus while improving the safety profile of the resulting OV. We review, 1) the engineering of chimeric OVs used in the treatment of HGG; 2) potential for a novel chimeric virotherapy in which the SARS-CoV-2 glycoprotein spike can be used to deliver OV therapy intranasally; and 3) areas which warrant further investigation to develop this approach for clinical use. METHODS: We performed an extensive review of chimeric OVs and specific modifications engineered to optimize safety and efficacy. Additionally, we assessed potential to use these principals to engineer the SARS-CoV-2 glycoprotein spike onto a non-pathogenic, replication competent virus to yield a novel chimeric for noninvasive, intranasal delivery. RESULTS: Viruses with pathogenic properties in wild-type have been successfully used as components of OVs and have demonstrated potential in both preclinical and clinical trials. Outcomes show that despite wild-type virulence, notable toxicities were not observed in clinical trials, highlighting the potential of viral pseudotyping as a safe therapeutic approach. CONCLUSIONS: The proposed method to utilize the SARS-CoV-2 glycoprotein in a novel chimeric poses advantages including 1) potential for non-invasive delivery, 2) therapy without need for maximal or uniform tumor coverage due to replication competence, 3) ability to reach infiltrative glioma cells, 4) potential to reach the brainstem, and 5) stimulation of host immunity through tumor cell lysis and antigen presentation |
format | Online Article Text |
id | pubmed-7650446 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-76504462020-12-09 COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA Immidisetti, Amanda Munier, Sean Patel, Nitesh Neuro Oncol Covid-19 and Neuro-Oncology BACKGROUND: High-grade gliomas (HGG) pose therapeutic challenges stemming from blood brain barrier, infiltrative growth, suppressed immune function, and tumor heterogeneity. Oncolytic viruses (OVs) are gaining traction for addressing these challenges. There is evidence that the SARS-CoV-2 glycoprotein spike binds the ACE-2 receptor in nasal epithelium and reaches the brainstem and thalamus via axonal transport through the olfactory pathway, making it an attractive candidate for OV therapy. Prior studies on chimerization of pathogenic virus-derived glycoprotein spikes with non-pathogenic strains exploit neurotropism of a wild-type virus while improving the safety profile of the resulting OV. We review, 1) the engineering of chimeric OVs used in the treatment of HGG; 2) potential for a novel chimeric virotherapy in which the SARS-CoV-2 glycoprotein spike can be used to deliver OV therapy intranasally; and 3) areas which warrant further investigation to develop this approach for clinical use. METHODS: We performed an extensive review of chimeric OVs and specific modifications engineered to optimize safety and efficacy. Additionally, we assessed potential to use these principals to engineer the SARS-CoV-2 glycoprotein spike onto a non-pathogenic, replication competent virus to yield a novel chimeric for noninvasive, intranasal delivery. RESULTS: Viruses with pathogenic properties in wild-type have been successfully used as components of OVs and have demonstrated potential in both preclinical and clinical trials. Outcomes show that despite wild-type virulence, notable toxicities were not observed in clinical trials, highlighting the potential of viral pseudotyping as a safe therapeutic approach. CONCLUSIONS: The proposed method to utilize the SARS-CoV-2 glycoprotein in a novel chimeric poses advantages including 1) potential for non-invasive delivery, 2) therapy without need for maximal or uniform tumor coverage due to replication competence, 3) ability to reach infiltrative glioma cells, 4) potential to reach the brainstem, and 5) stimulation of host immunity through tumor cell lysis and antigen presentation Oxford University Press 2020-11-09 /pmc/articles/PMC7650446/ http://dx.doi.org/10.1093/neuonc/noaa215.101 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) |
spellingShingle | Covid-19 and Neuro-Oncology Immidisetti, Amanda Munier, Sean Patel, Nitesh COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA |
title | COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA |
title_full | COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA |
title_fullStr | COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA |
title_full_unstemmed | COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA |
title_short | COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA |
title_sort | covd-18. potential to harness sars-cov-2 neurotropism in the delivery of oncolytic virotherapy for the treatment of high-grade glioma |
topic | Covid-19 and Neuro-Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650446/ http://dx.doi.org/10.1093/neuonc/noaa215.101 |
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