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Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators
Enadenotucirev (EnAd) is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinic...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363721/ https://www.ncbi.nlm.nih.gov/pubmed/28345021 http://dx.doi.org/10.1016/j.omto.2016.11.003 |
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author | Dyer, Arthur Di, Ying Calderon, Hugo Illingworth, Sam Kueberuwa, Gray Tedcastle, Alison Jakeman, Phil Chia, Suet Lin Brown, Alice Silva, Michael A. Barlow, David Beadle, John Hermiston, Terry Ferguson, David J.P. Champion, Brian Fisher, Kerry D. Seymour, Leonard W. |
author_facet | Dyer, Arthur Di, Ying Calderon, Hugo Illingworth, Sam Kueberuwa, Gray Tedcastle, Alison Jakeman, Phil Chia, Suet Lin Brown, Alice Silva, Michael A. Barlow, David Beadle, John Hermiston, Terry Ferguson, David J.P. Champion, Brian Fisher, Kerry D. Seymour, Leonard W. |
author_sort | Dyer, Arthur |
collection | PubMed |
description | Enadenotucirev (EnAd) is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinical trials. EnAd kills cells more quickly than type 5 adenovirus, and speed of cytotoxicity is dose dependent. The EnAd death pathway does not involve p53, is predominantly caspase independent, and appears to involve a rapid fall in cellular ATP. Infected cells show early loss of membrane integrity; increased exposure of calreticulin; extracellular release of ATP, HSP70, and HMGB1; and influx of calcium. The virus also causes an obvious single membrane blister reminiscent of ischemic cell death by oncosis. In human tumor biopsies maintained in ex vivo culture, EnAd mediated release of pro-inflammatory mediators such as TNF-α, IL-6, and HMGB1. In accordance with this, EnAd-infected tumor cells showed potent stimulation of dendritic cells and CD4(+) T cells in a mixed tumor-leukocyte reaction in vitro. Whereas many viruses have evolved for efficient propagation with minimal inflammation, bioselection of EnAd for rapid killing has yielded a virus with a short life cycle that combines potent cytotoxicity with a proinflammatory mechanism of cell death. |
format | Online Article Text |
id | pubmed-5363721 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-53637212017-03-24 Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators Dyer, Arthur Di, Ying Calderon, Hugo Illingworth, Sam Kueberuwa, Gray Tedcastle, Alison Jakeman, Phil Chia, Suet Lin Brown, Alice Silva, Michael A. Barlow, David Beadle, John Hermiston, Terry Ferguson, David J.P. Champion, Brian Fisher, Kerry D. Seymour, Leonard W. Mol Ther Oncolytics Original Article Enadenotucirev (EnAd) is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinical trials. EnAd kills cells more quickly than type 5 adenovirus, and speed of cytotoxicity is dose dependent. The EnAd death pathway does not involve p53, is predominantly caspase independent, and appears to involve a rapid fall in cellular ATP. Infected cells show early loss of membrane integrity; increased exposure of calreticulin; extracellular release of ATP, HSP70, and HMGB1; and influx of calcium. The virus also causes an obvious single membrane blister reminiscent of ischemic cell death by oncosis. In human tumor biopsies maintained in ex vivo culture, EnAd mediated release of pro-inflammatory mediators such as TNF-α, IL-6, and HMGB1. In accordance with this, EnAd-infected tumor cells showed potent stimulation of dendritic cells and CD4(+) T cells in a mixed tumor-leukocyte reaction in vitro. Whereas many viruses have evolved for efficient propagation with minimal inflammation, bioselection of EnAd for rapid killing has yielded a virus with a short life cycle that combines potent cytotoxicity with a proinflammatory mechanism of cell death. American Society of Gene & Cell Therapy 2016-12-10 /pmc/articles/PMC5363721/ /pubmed/28345021 http://dx.doi.org/10.1016/j.omto.2016.11.003 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Article Dyer, Arthur Di, Ying Calderon, Hugo Illingworth, Sam Kueberuwa, Gray Tedcastle, Alison Jakeman, Phil Chia, Suet Lin Brown, Alice Silva, Michael A. Barlow, David Beadle, John Hermiston, Terry Ferguson, David J.P. Champion, Brian Fisher, Kerry D. Seymour, Leonard W. Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators |
title | Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators |
title_full | Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators |
title_fullStr | Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators |
title_full_unstemmed | Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators |
title_short | Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators |
title_sort | oncolytic group b adenovirus enadenotucirev mediates non-apoptotic cell death with membrane disruption and release of inflammatory mediators |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363721/ https://www.ncbi.nlm.nih.gov/pubmed/28345021 http://dx.doi.org/10.1016/j.omto.2016.11.003 |
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