Cargando…
In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics
Tumor therapy with replication competent viruses is an exciting approach to cancer eradication where viruses are engineered to specifically infect, replicate, spread and kill tumor cells. The outcome of tumor virotherapy is complex due to the variable interactions between the cancer cell and virus p...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400333/ https://www.ncbi.nlm.nih.gov/pubmed/30835721 http://dx.doi.org/10.1371/journal.pcbi.1006773 |
_version_ | 1783399931815395328 |
---|---|
author | Berg, David R. Offord, Chetan P. Kemler, Iris Ennis, Matthew K. Chang, Lawrence Paulik, George Bajzer, Zeljko Neuhauser, Claudia Dingli, David |
author_facet | Berg, David R. Offord, Chetan P. Kemler, Iris Ennis, Matthew K. Chang, Lawrence Paulik, George Bajzer, Zeljko Neuhauser, Claudia Dingli, David |
author_sort | Berg, David R. |
collection | PubMed |
description | Tumor therapy with replication competent viruses is an exciting approach to cancer eradication where viruses are engineered to specifically infect, replicate, spread and kill tumor cells. The outcome of tumor virotherapy is complex due to the variable interactions between the cancer cell and virus populations as well as the immune response. Oncolytic viruses are highly efficient in killing tumor cells in vitro, especially in a 2D monolayer of tumor cells, their efficiency is significantly lower in a 3D environment, both in vitro and in vivo. This indicates that the spatial dimension may have a major influence on the dynamics of virus spread. We study the dynamic behavior of a spatially explicit computational model of tumor and virus interactions using a combination of in vitro 2D and 3D experimental studies to inform the models. We determine the number of nearest neighbor tumor cells in 2D (median = 6) and 3D tumor spheroids (median = 16) and how this influences virus spread and the outcome of therapy. The parameter range leading to tumor eradication is small and even harder to achieve in 3D. The lower efficiency in 3D exists despite the presence of many more adjacent cells in the 3D environment that results in a shorter time to reach equilibrium. The mean field mathematical models generally used to describe tumor virotherapy appear to provide an overoptimistic view of the outcomes of therapy. Three dimensional space provides a significant barrier to efficient and complete virus spread within tumors and needs to be explicitly taken into account for virus optimization to achieve the desired outcome of therapy. |
format | Online Article Text |
id | pubmed-6400333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-64003332019-03-17 In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics Berg, David R. Offord, Chetan P. Kemler, Iris Ennis, Matthew K. Chang, Lawrence Paulik, George Bajzer, Zeljko Neuhauser, Claudia Dingli, David PLoS Comput Biol Research Article Tumor therapy with replication competent viruses is an exciting approach to cancer eradication where viruses are engineered to specifically infect, replicate, spread and kill tumor cells. The outcome of tumor virotherapy is complex due to the variable interactions between the cancer cell and virus populations as well as the immune response. Oncolytic viruses are highly efficient in killing tumor cells in vitro, especially in a 2D monolayer of tumor cells, their efficiency is significantly lower in a 3D environment, both in vitro and in vivo. This indicates that the spatial dimension may have a major influence on the dynamics of virus spread. We study the dynamic behavior of a spatially explicit computational model of tumor and virus interactions using a combination of in vitro 2D and 3D experimental studies to inform the models. We determine the number of nearest neighbor tumor cells in 2D (median = 6) and 3D tumor spheroids (median = 16) and how this influences virus spread and the outcome of therapy. The parameter range leading to tumor eradication is small and even harder to achieve in 3D. The lower efficiency in 3D exists despite the presence of many more adjacent cells in the 3D environment that results in a shorter time to reach equilibrium. The mean field mathematical models generally used to describe tumor virotherapy appear to provide an overoptimistic view of the outcomes of therapy. Three dimensional space provides a significant barrier to efficient and complete virus spread within tumors and needs to be explicitly taken into account for virus optimization to achieve the desired outcome of therapy. Public Library of Science 2019-03-05 /pmc/articles/PMC6400333/ /pubmed/30835721 http://dx.doi.org/10.1371/journal.pcbi.1006773 Text en © 2019 Berg et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Berg, David R. Offord, Chetan P. Kemler, Iris Ennis, Matthew K. Chang, Lawrence Paulik, George Bajzer, Zeljko Neuhauser, Claudia Dingli, David In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics |
title | In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics |
title_full | In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics |
title_fullStr | In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics |
title_full_unstemmed | In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics |
title_short | In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics |
title_sort | in vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400333/ https://www.ncbi.nlm.nih.gov/pubmed/30835721 http://dx.doi.org/10.1371/journal.pcbi.1006773 |
work_keys_str_mv | AT bergdavidr invitroandinsilicomultidimensionalmodelingofoncolytictumorvirotherapydynamics AT offordchetanp invitroandinsilicomultidimensionalmodelingofoncolytictumorvirotherapydynamics AT kemleriris invitroandinsilicomultidimensionalmodelingofoncolytictumorvirotherapydynamics AT ennismatthewk invitroandinsilicomultidimensionalmodelingofoncolytictumorvirotherapydynamics AT changlawrence invitroandinsilicomultidimensionalmodelingofoncolytictumorvirotherapydynamics AT paulikgeorge invitroandinsilicomultidimensionalmodelingofoncolytictumorvirotherapydynamics AT bajzerzeljko invitroandinsilicomultidimensionalmodelingofoncolytictumorvirotherapydynamics AT neuhauserclaudia invitroandinsilicomultidimensionalmodelingofoncolytictumorvirotherapydynamics AT dinglidavid invitroandinsilicomultidimensionalmodelingofoncolytictumorvirotherapydynamics |