Mathematical modeling of a hypoxia-regulated enclitic virus delivered by tumor-associated macrophages
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. Tumo...
| Main Authors: | , |
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| Format: | Journal article |
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Elsevier
2018
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| _version_ | 1797079793776197632 |
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| author | Boemo, M Byrne, H |
| author_facet | Boemo, M Byrne, H |
| author_sort | Boemo, M |
| collection | OXFORD |
| description | 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. Tumourassociated 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. |
| first_indexed | 2024-03-07T00:50:51Z |
| format | Journal article |
| id | oxford-uuid:865a9aa1-98f5-446b-b902-503833021c19 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:50:51Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:865a9aa1-98f5-446b-b902-503833021c192022-03-26T22:03:27ZMathematical modeling of a hypoxia-regulated enclitic virus delivered by tumor-associated macrophagesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:865a9aa1-98f5-446b-b902-503833021c19Symplectic Elements at OxfordElsevier2018Boemo, MByrne, HTumour 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. Tumourassociated 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. |
| spellingShingle | Boemo, M Byrne, H Mathematical modeling of a hypoxia-regulated enclitic virus delivered by tumor-associated macrophages |
| title | Mathematical modeling of a hypoxia-regulated enclitic virus delivered by tumor-associated macrophages |
| title_full | Mathematical modeling of a hypoxia-regulated enclitic virus delivered by tumor-associated macrophages |
| title_fullStr | Mathematical modeling of a hypoxia-regulated enclitic virus delivered by tumor-associated macrophages |
| title_full_unstemmed | Mathematical modeling of a hypoxia-regulated enclitic virus delivered by tumor-associated macrophages |
| title_short | Mathematical modeling of a hypoxia-regulated enclitic virus delivered by tumor-associated macrophages |
| title_sort | mathematical modeling of a hypoxia regulated enclitic virus delivered by tumor associated macrophages |
| work_keys_str_mv | AT boemom mathematicalmodelingofahypoxiaregulatedencliticvirusdeliveredbytumorassociatedmacrophages AT byrneh mathematicalmodelingofahypoxiaregulatedencliticvirusdeliveredbytumorassociatedmacrophages |