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Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice
Vaccinia viruses (VACV) are a novel class of immune-oncolytic therapeutics and their mechanism of action is based both on their capacity to replicate selectively in cancer cells and to elicit danger signals that can boost anti-tumor immunity. We recently reported that the intratumor expression of ML...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458643/ https://www.ncbi.nlm.nih.gov/pubmed/32923163 http://dx.doi.org/10.1080/2162402X.2020.1802968 |
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author | Van Hoecke, Lien Riederer, Stephanie Saelens, Xavier Sutter, Gerd Rojas, Juan J. |
author_facet | Van Hoecke, Lien Riederer, Stephanie Saelens, Xavier Sutter, Gerd Rojas, Juan J. |
author_sort | Van Hoecke, Lien |
collection | PubMed |
description | Vaccinia viruses (VACV) are a novel class of immune-oncolytic therapeutics and their mechanism of action is based both on their capacity to replicate selectively in cancer cells and to elicit danger signals that can boost anti-tumor immunity. We recently reported that the intratumor expression of MLKL, a necroptosis inducing factor, generates a protective anti-tumor immunity. Here, we combined both approaches to test the use of VACV to deliver MLKL into the tumor. We generated VACV vectors expressing MLKL and evaluated the effects of MLKL on antitumor efficacy. In vitro infection of cancer cells with MLKL-expressing vectors led to cell death with necroptotic hallmarks. In syngeneic mouse tumor models, VACV expressing MLKL induced an outstanding antitumor activity, which was associated with a robust immunity directed against neo-epitopes. In conclusion, delivery of MLKL by VACV vectors boosts the intrinsic anti-tumor properties of these viral vectors by promoting in situ immunogenic cell death of infected cancer cells. |
format | Online Article Text |
id | pubmed-7458643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-74586432020-09-11 Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice Van Hoecke, Lien Riederer, Stephanie Saelens, Xavier Sutter, Gerd Rojas, Juan J. Oncoimmunology Brief Report Vaccinia viruses (VACV) are a novel class of immune-oncolytic therapeutics and their mechanism of action is based both on their capacity to replicate selectively in cancer cells and to elicit danger signals that can boost anti-tumor immunity. We recently reported that the intratumor expression of MLKL, a necroptosis inducing factor, generates a protective anti-tumor immunity. Here, we combined both approaches to test the use of VACV to deliver MLKL into the tumor. We generated VACV vectors expressing MLKL and evaluated the effects of MLKL on antitumor efficacy. In vitro infection of cancer cells with MLKL-expressing vectors led to cell death with necroptotic hallmarks. In syngeneic mouse tumor models, VACV expressing MLKL induced an outstanding antitumor activity, which was associated with a robust immunity directed against neo-epitopes. In conclusion, delivery of MLKL by VACV vectors boosts the intrinsic anti-tumor properties of these viral vectors by promoting in situ immunogenic cell death of infected cancer cells. Taylor & Francis 2020-08-20 /pmc/articles/PMC7458643/ /pubmed/32923163 http://dx.doi.org/10.1080/2162402X.2020.1802968 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Brief Report Van Hoecke, Lien Riederer, Stephanie Saelens, Xavier Sutter, Gerd Rojas, Juan J. Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice |
title | Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice |
title_full | Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice |
title_fullStr | Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice |
title_full_unstemmed | Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice |
title_short | Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice |
title_sort | recombinant viruses delivering the necroptosis mediator mlkl induce a potent antitumor immunity in mice |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458643/ https://www.ncbi.nlm.nih.gov/pubmed/32923163 http://dx.doi.org/10.1080/2162402X.2020.1802968 |
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