Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing virus therapeutics
The past century's description of oncolytic virotherapy as a cancer treatment involving specially-engineered viruses that exploit immune deficiencies to selectively lyse cancer cells is no longer adequate. Some of the most promising therapeutic candidates are now being engineered to produce im...
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| Format: | Article |
| Language: | English |
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AIMS Press
2015-03-01
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| Series: | Mathematical Biosciences and Engineering |
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| Online Access: | https://www.aimspress.com/article/doi/10.3934/mbe.2015.12.841 |
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| author | Peter S. Kim Joseph J. Crivelli Il-Kyu Choi Chae-Ok Yun Joanna R. Wares |
| author_facet | Peter S. Kim Joseph J. Crivelli Il-Kyu Choi Chae-Ok Yun Joanna R. Wares |
| author_sort | Peter S. Kim |
| collection | DOAJ |
| description | The past century's description of oncolytic virotherapy as a cancer treatment involving specially-engineered viruses that exploit immune deficiencies to selectively lyse cancer cells is no longer adequate. Some of the most promising therapeutic candidates are now being engineered to produce immunostimulatory factors, such as cytokines and co-stimulatory molecules, which, in addition to viral oncolysis, initiate a cytotoxic immune attack against the tumor. This study addresses the combined effects of viral oncolysis and T-cell-mediated oncolysis. We employ a mathematical model of virotherapy that induces release of cytokine IL-12 and co-stimulatory molecule 4-1BB ligand. We found that the model closely matches previously published data, and while viral oncolysis is fundamental in reducing tumor burden, increased stimulation of cytotoxic T cells leads to a short-term reduction in tumor size, but a faster relapse. In addition, we found that combinations of specialist viruses that express either IL-12 or 4-1BBL might initially act more potently against tumors than a generalist virus that simultaneously expresses both, but the advantage is likely not large enough to replace treatment using the generalist virus. Finally, according to our model and its current assumptions, virotherapy appears to be optimizable through targeted design and treatment combinations to substantially improve therapeutic outcomes. |
| format | Article |
| id | doaj-art-d355eeb9a46847beb9ff63d9580c54c7 |
| institution | Kabale University |
| issn | 1551-0018 |
| language | English |
| publishDate | 2015-03-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | Mathematical Biosciences and Engineering |
| spelling | doaj-art-d355eeb9a46847beb9ff63d9580c54c72025-01-24T02:32:12ZengAIMS PressMathematical Biosciences and Engineering1551-00182015-03-0112484185810.3934/mbe.2015.12.841Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing virus therapeuticsPeter S. Kim0Joseph J. Crivelli1Il-Kyu Choi2Chae-Ok Yun3Joanna R. Wares4School of Mathematics and Statistics, University of Sydney, Sydney, NSWWeill Cornell Medical College, New York, NYDepartment of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791Department of Bioengineering, College of Engineering, Hanyang University, SeoulDepartment of Mathematics and Computer Science, University of Richmond, Richmond, VAThe past century's description of oncolytic virotherapy as a cancer treatment involving specially-engineered viruses that exploit immune deficiencies to selectively lyse cancer cells is no longer adequate. Some of the most promising therapeutic candidates are now being engineered to produce immunostimulatory factors, such as cytokines and co-stimulatory molecules, which, in addition to viral oncolysis, initiate a cytotoxic immune attack against the tumor. This study addresses the combined effects of viral oncolysis and T-cell-mediated oncolysis. We employ a mathematical model of virotherapy that induces release of cytokine IL-12 and co-stimulatory molecule 4-1BB ligand. We found that the model closely matches previously published data, and while viral oncolysis is fundamental in reducing tumor burden, increased stimulation of cytotoxic T cells leads to a short-term reduction in tumor size, but a faster relapse. In addition, we found that combinations of specialist viruses that express either IL-12 or 4-1BBL might initially act more potently against tumors than a generalist virus that simultaneously expresses both, but the advantage is likely not large enough to replace treatment using the generalist virus. Finally, according to our model and its current assumptions, virotherapy appears to be optimizable through targeted design and treatment combinations to substantially improve therapeutic outcomes.https://www.aimspress.com/article/doi/10.3934/mbe.2015.12.841co-stimulatory moleculesadenovirusordinary differential equations model.mathematical modelcytokinesoncolytic virotherapy |
| spellingShingle | Peter S. Kim Joseph J. Crivelli Il-Kyu Choi Chae-Ok Yun Joanna R. Wares Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing virus therapeutics Mathematical Biosciences and Engineering co-stimulatory molecules adenovirus ordinary differential equations model. mathematical model cytokines oncolytic virotherapy |
| title | Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing virus therapeutics |
| title_full | Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing virus therapeutics |
| title_fullStr | Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing virus therapeutics |
| title_full_unstemmed | Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing virus therapeutics |
| title_short | Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing virus therapeutics |
| title_sort | quantitative impact of immunomodulation versus oncolysis with cytokine expressing virus therapeutics |
| topic | co-stimulatory molecules adenovirus ordinary differential equations model. mathematical model cytokines oncolytic virotherapy |
| url | https://www.aimspress.com/article/doi/10.3934/mbe.2015.12.841 |
| work_keys_str_mv | AT peterskim quantitativeimpactofimmunomodulationversusoncolysiswithcytokineexpressingvirustherapeutics AT josephjcrivelli quantitativeimpactofimmunomodulationversusoncolysiswithcytokineexpressingvirustherapeutics AT ilkyuchoi quantitativeimpactofimmunomodulationversusoncolysiswithcytokineexpressingvirustherapeutics AT chaeokyun quantitativeimpactofimmunomodulationversusoncolysiswithcytokineexpressingvirustherapeutics AT joannarwares quantitativeimpactofimmunomodulationversusoncolysiswithcytokineexpressingvirustherapeutics |