Mathematical modelling of a hypoxia-regulated oncolytic virus delivered by tumour-associated macrophages
Copyright © 2018. Published by Elsevier Ltd..
Tumour hypoxia has long presented a challenge for cancer therapy: Poor vascularisation in hypoxic regions hinders both the delivery of chemotherapeutic agents and the response to radiotherapy, and hypoxic cancer cells that survive treatment can trigger tumour regrowth after treatment has ended. Tumour-associated macrophages are attractive vehicles for drug delivery because they localise in hypoxic areas of the tumour. In this paper, we derive a mathematical model for the infiltration of an in vitro tumour spheroid by macrophages that have been engineered to release an oncolytic adenovirus under hypoxic conditions. We use this model to predict the efficacy of treatment schedules in which radiotherapy and the engineered macrophages are given in combination. Our work suggests that engineered macrophages should be introduced immediately after radiotherapy for maximum treatment efficacy. Our model provides a framework that may guide future experiments to determine how multiple rounds of radiotherapy and macrophage virotherapy should be coordinated to maximise therapeutic responses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:461 |
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| Enthalten in: |
Journal of theoretical biology - 461(2019) vom: 14. Jan., Seite 102-116 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Boemo, Michael A [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 23.03.2020 Date Revised 10.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jtbi.2018.10.044 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM289937116 |
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| 500 | |a Date Revised 10.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018. Published by Elsevier Ltd. | ||
| 520 | |a Tumour hypoxia has long presented a challenge for cancer therapy: Poor vascularisation in hypoxic regions hinders both the delivery of chemotherapeutic agents and the response to radiotherapy, and hypoxic cancer cells that survive treatment can trigger tumour regrowth after treatment has ended. Tumour-associated macrophages are attractive vehicles for drug delivery because they localise in hypoxic areas of the tumour. In this paper, we derive a mathematical model for the infiltration of an in vitro tumour spheroid by macrophages that have been engineered to release an oncolytic adenovirus under hypoxic conditions. We use this model to predict the efficacy of treatment schedules in which radiotherapy and the engineered macrophages are given in combination. Our work suggests that engineered macrophages should be introduced immediately after radiotherapy for maximum treatment efficacy. Our model provides a framework that may guide future experiments to determine how multiple rounds of radiotherapy and macrophage virotherapy should be coordinated to maximise therapeutic responses | ||
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| 650 | 4 | |a Oncolytic adenovirus | |
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| 650 | 4 | |a Tumour-associated macrophages | |
| 700 | 1 | |a Byrne, Helen M |e verfasserin |4 aut | |
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