An Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma

Oncolytic viral therapies and immunotherapies are of growing clinical interest due to their selectivity for tumor cells over healthy cells and their immunostimulatory properties. These treatment modalities provide promising alternatives to the standard of care, particularly for cancers with poor pro...

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Autores principales:	Kathleen M. Storey, Trachette L. Jackson
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mathematical modeling agent-based modeling oncolytic viral therapy immune checkpoint inhibitor combination therapy glioblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0a382b4a66f94026b9897491d6da4ce9
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spelling	oai:doaj.org-article:0a382b4a66f94026b9897491d6da4ce92021-11-11T15:28:06ZAn Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma10.3390/cancers132153142072-6694https://doaj.org/article/0a382b4a66f94026b9897491d6da4ce92021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5314https://doaj.org/toc/2072-6694Oncolytic viral therapies and immunotherapies are of growing clinical interest due to their selectivity for tumor cells over healthy cells and their immunostimulatory properties. These treatment modalities provide promising alternatives to the standard of care, particularly for cancers with poor prognoses, such as the lethal brain tumor glioblastoma (GBM). However, uncertainty remains regarding optimal dosing strategies, including how the spatial location of viral doses impacts therapeutic efficacy and tumor landscape characteristics that are most conducive to producing an effective immune response. We develop a three-dimensional agent-based model (ABM) of GBM undergoing treatment with a combination of an oncolytic Herpes Simplex Virus and an anti-PD-1 immunotherapy. We use a mechanistic approach to model the interactions between distinct populations of immune cells, incorporating both innate and adaptive immune responses to oncolytic viral therapy and including a mechanism of adaptive immune suppression via the PD-1/PD-L1 checkpoint pathway. We utilize the spatially explicit nature of the ABM to determine optimal viral dosing in both the temporal and spatial contexts. After proposing an adaptive viral dosing strategy that chooses to dose sites at the location of highest tumor cell density, we find that, in most cases, this adaptive strategy produces a more effective treatment outcome than repeatedly dosing in the center of the tumor.Kathleen M. StoreyTrachette L. JacksonMDPI AGarticlemathematical modelingagent-based modelingoncolytic viral therapyimmune checkpoint inhibitorcombination therapyglioblastomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5314, p 5314 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mathematical modeling agent-based modeling oncolytic viral therapy immune checkpoint inhibitor combination therapy glioblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	mathematical modeling agent-based modeling oncolytic viral therapy immune checkpoint inhibitor combination therapy glioblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Kathleen M. Storey Trachette L. Jackson An Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma
description	Oncolytic viral therapies and immunotherapies are of growing clinical interest due to their selectivity for tumor cells over healthy cells and their immunostimulatory properties. These treatment modalities provide promising alternatives to the standard of care, particularly for cancers with poor prognoses, such as the lethal brain tumor glioblastoma (GBM). However, uncertainty remains regarding optimal dosing strategies, including how the spatial location of viral doses impacts therapeutic efficacy and tumor landscape characteristics that are most conducive to producing an effective immune response. We develop a three-dimensional agent-based model (ABM) of GBM undergoing treatment with a combination of an oncolytic Herpes Simplex Virus and an anti-PD-1 immunotherapy. We use a mechanistic approach to model the interactions between distinct populations of immune cells, incorporating both innate and adaptive immune responses to oncolytic viral therapy and including a mechanism of adaptive immune suppression via the PD-1/PD-L1 checkpoint pathway. We utilize the spatially explicit nature of the ABM to determine optimal viral dosing in both the temporal and spatial contexts. After proposing an adaptive viral dosing strategy that chooses to dose sites at the location of highest tumor cell density, we find that, in most cases, this adaptive strategy produces a more effective treatment outcome than repeatedly dosing in the center of the tumor.
format	article
author	Kathleen M. Storey Trachette L. Jackson
author_facet	Kathleen M. Storey Trachette L. Jackson
author_sort	Kathleen M. Storey
title	An Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma
title_short	An Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma
title_full	An Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma
title_fullStr	An Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma
title_full_unstemmed	An Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma
title_sort	agent-based model of combination oncolytic viral therapy and anti-pd-1 immunotherapy reveals the importance of spatial location when treating glioblastoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0a382b4a66f94026b9897491d6da4ce9
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An Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma

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