The Optimal Balance between Oncolytic Viruses and Natural Killer Cells: A Mathematical Approach
Oncolytic virotherapy (OV) is a cancer therapy utilizing lytic viruses that specifically target cancer cells for elimination. In this relatively new therapy, two contradictory observations have been made. Some studies showed that immune responses including activated natural killer (NK) cells post on...
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Published in | Mathematics (Basel) Vol. 10; no. 18; p. 3370 |
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Abstract | Oncolytic virotherapy (OV) is a cancer therapy utilizing lytic viruses that specifically target cancer cells for elimination. In this relatively new therapy, two contradictory observations have been made. Some studies showed that immune responses including activated natural killer (NK) cells post oncolytic viral infection increased the cancer cell death, while others reported that such initial immune responses diminished the anti-tumor efficacy, which was caused by premature viral clearance. In this paper, we present a mathematical model to investigate the effect of NK cells on oncolytic virotherapy. Particularly, we focused on the minimum condition for NK cells to be activated in terms of parameters and how the activation of NK cells interacts and changes the dynamics among cancer, infected cancer cells and oncolytic virus. Analytic works for the existence and stability conditions of equilibrium points are provided. Numerical results are in good agreement with analytic solutions. Our numerical results show that equilibrium points can be created or destroyed by the activation of NK cells in a dynamical system and suggest that the balance between the bursting rate of the virus and the activation rate of NK cells is a crucial factor for successful OV therapy. |
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AbstractList | Oncolytic virotherapy (OV) is a cancer therapy utilizing lytic viruses that specifically target cancer cells for elimination. In this relatively new therapy, two contradictory observations have been made. Some studies showed that immune responses including activated natural killer (NK) cells post oncolytic viral infection increased the cancer cell death, while others reported that such initial immune responses diminished the anti-tumor efficacy, which was caused by premature viral clearance. In this paper, we present a mathematical model to investigate the effect of NK cells on oncolytic virotherapy. Particularly, we focused on the minimum condition for NK cells to be activated in terms of parameters and how the activation of NK cells interacts and changes the dynamics among cancer, infected cancer cells and oncolytic virus. Analytic works for the existence and stability conditions of equilibrium points are provided. Numerical results are in good agreement with analytic solutions. Our numerical results show that equilibrium points can be created or destroyed by the activation of NK cells in a dynamical system and suggest that the balance between the bursting rate of the virus and the activation rate of NK cells is a crucial factor for successful OV therapy. |
Audience | Academic |
Author | Sung, Chang K Kim, Dongwook Shin, Dong-Hoon |
Author_xml | – sequence: 1 fullname: Kim, Dongwook – sequence: 2 fullname: Shin, Dong-Hoon – sequence: 3 fullname: Sung, Chang K |
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Cites_doi | 10.1038/cgt.2008.74 10.3934/mbe.2011.8.841 10.1155/2017/6587258 10.1016/j.jtbi.2015.04.004 10.1038/s41598-019-57240-x 10.1172/JCI32727 10.11594/jtls.07.01.03 10.3390/v13081570 10.1080/21645515.2020.1723363 10.3389/fonc.2017.00106 10.1056/NEJMoa1716435 10.3390/cancers13061383 10.3390/v13081450 10.1038/nri2448 10.1158/1535-7163.MCT-05-0334 10.1073/pnas.1715295115 10.1186/s13662-020-02893-6 10.3389/fimmu.2020.00683 10.1016/j.omtm.2020.01.001 10.1038/nm.3013 10.1089/104303403321070847 10.1038/mt.2011.276 10.3389/fonc.2020.00702 10.1016/j.semcancer.2021.05.013 10.1007/s11538-021-00903-6 10.1158/0008-5472.CAN-04-3227 10.1016/j.omto.2020.02.001 10.1158/0008-5472.CAN-05-2661 10.3390/cancers10100356 10.1158/1078-0432.CCR-16-0477 |
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SubjectTerms | Adenoviruses Anticancer properties bifurcation Cancer Cancer therapies Cell death dynamical system Equilibrium Exact solutions Food science Immune system Immunotherapy Killer cells mathematical model Mathematical models Mathematical research NK cells oncolytic virotherapy Poliomyelitis Population Stability analysis Therapy Viral infections Viruses |
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