Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | LOCUS Repositório Institucional da UFV |
Texto Completo: | https://doi.org/10.1088/1478-3975/10/2/025005 http://www.locus.ufv.br/handle/123456789/19501 |
Resumo: | Oncolytic virotherapy—the use of viruses that specifically kill tumor cells—is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In this paper, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD8 + T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice. |
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Paiva, Leticia R .Silva, Hallan S.Ferreira, Silvio C.Martins, Marcelo L.2018-05-11T14:04:18Z2018-05-11T14:04:18Z2013-03-1514783975https://doi.org/10.1088/1478-3975/10/2/025005http://www.locus.ufv.br/handle/123456789/19501Oncolytic virotherapy—the use of viruses that specifically kill tumor cells—is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In this paper, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD8 + T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.engPhysical Biologyv. 10, p. 025005, March 2013IOP Publishing Ltdinfo:eu-repo/semantics/openAccessViral therapyImmunity suppressionMultiscale model for the effects of adaptive immunity suppression on the viral therapy of cancerinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfreponame:LOCUS Repositório Institucional da UFVinstname:Universidade Federal de Viçosa (UFV)instacron:UFVORIGINALartigo.pdfartigo.pdfTexto completoapplication/pdf567954https://locus.ufv.br//bitstream/123456789/19501/1/artigo.pdff8a80afcd70f7d76d276981c02bf68f5MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://locus.ufv.br//bitstream/123456789/19501/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52THUMBNAILartigo.pdf.jpgartigo.pdf.jpgIM Thumbnailimage/jpeg3894https://locus.ufv.br//bitstream/123456789/19501/3/artigo.pdf.jpg07a78673376c6b1f28953a1b3a91bf87MD53123456789/195012018-05-11 23:00:51.095oai:locus.ufv.br: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Repositório InstitucionalPUBhttps://www.locus.ufv.br/oai/requestfabiojreis@ufv.bropendoar:21452018-05-12T02:00:51LOCUS Repositório Institucional da UFV - Universidade Federal de Viçosa (UFV)false |
dc.title.en.fl_str_mv |
Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer |
title |
Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer |
spellingShingle |
Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer Paiva, Leticia R . Viral therapy Immunity suppression |
title_short |
Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer |
title_full |
Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer |
title_fullStr |
Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer |
title_full_unstemmed |
Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer |
title_sort |
Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer |
author |
Paiva, Leticia R . |
author_facet |
Paiva, Leticia R . Silva, Hallan S. Ferreira, Silvio C. Martins, Marcelo L. |
author_role |
author |
author2 |
Silva, Hallan S. Ferreira, Silvio C. Martins, Marcelo L. |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Paiva, Leticia R . Silva, Hallan S. Ferreira, Silvio C. Martins, Marcelo L. |
dc.subject.pt-BR.fl_str_mv |
Viral therapy Immunity suppression |
topic |
Viral therapy Immunity suppression |
description |
Oncolytic virotherapy—the use of viruses that specifically kill tumor cells—is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In this paper, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD8 + T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-03-15 |
dc.date.accessioned.fl_str_mv |
2018-05-11T14:04:18Z |
dc.date.available.fl_str_mv |
2018-05-11T14:04:18Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.1088/1478-3975/10/2/025005 http://www.locus.ufv.br/handle/123456789/19501 |
dc.identifier.issn.none.fl_str_mv |
14783975 |
identifier_str_mv |
14783975 |
url |
https://doi.org/10.1088/1478-3975/10/2/025005 http://www.locus.ufv.br/handle/123456789/19501 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofseries.pt-BR.fl_str_mv |
v. 10, p. 025005, March 2013 |
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IOP Publishing Ltd info:eu-repo/semantics/openAccess |
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IOP Publishing Ltd |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Physical Biology |
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Physical Biology |
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LOCUS Repositório Institucional da UFV |
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