Application of control theory in a delayed-infection and immune-evading oncolytic virotherapy

Taeyong Lee; Adrianne L. Jenner; Peter S. Kim; Jeehyun Lee; Taeyong Lee; Adrianne L. Jenner; Peter S. Kim; Jeehyun Lee

doi:10.3934/mbe.2020126

Mathematical Biosciences and Engineering

2020, Volume 17, Issue 3: 2361-2383. doi: 10.3934/mbe.2020126

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Application of control theory in a delayed-infection and immune-evading oncolytic virotherapy

1.
Department of Mathematics, College of Science, Yonsei University, Seoul, Korea
2.
Département de mathématiques et de statistique, Université de Montréal, Montréal, Canada
3.
School of Mathematics and Statistics, University of Sydney, Sydney, Australia
4.
Department of Computer Science & Engineering, Yonsei University, Seoul, Korea

Received: 16 December 2019 Accepted: 05 February 2020 Published: 12 February 2020

Oncolytic virotherapy is a promising cancer treatment that harnesses the power of viruses. Through genetic engineering, these viruses are cultivated to infect and destroy cancer cells. While this therapy has shown success in a range of clinical trials, an open problem in the field is to determine more effective perturbations of these viruses. In this work, we use a controlled therapy approach to determine the optimal treatment protocol for a delayed infection from an immune-evading, coated virus. We derive a system of partial differential equations to model the interaction between a growing tumour and this coated oncolytic virus. Using this system, we show that viruses with inhibited viral clearance and infectivity are more effective than uncoated viruses. We then consider a hierarchical level of coating that degrades over time and determine a nontrivial initial distribution of coating levels needed to produce the lowest tumour volume. Interestingly, we find that a bimodal mixture of thickly coated and thinly coated virus is necessary to achieve a minimum tumour size. Throughout this article we also consider the effects of immune clearance of the virus. We show how different immune responses instigate significantly different treatment outcomes.
- virus,
- oncolytic virotherapy,
- cancer,
- optimal control,
- partial differential equations
Citation: Taeyong Lee, Adrianne L. Jenner, Peter S. Kim, Jeehyun Lee. Application of control theory in a delayed-infection and immune-evading oncolytic virotherapy[J]. Mathematical Biosciences and Engineering, 2020, 17(3): 2361-2383. doi: 10.3934/mbe.2020126

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Abstract

Oncolytic virotherapy is a promising cancer treatment that harnesses the power of viruses. Through genetic engineering, these viruses are cultivated to infect and destroy cancer cells. While this therapy has shown success in a range of clinical trials, an open problem in the field is to determine more effective perturbations of these viruses. In this work, we use a controlled therapy approach to determine the optimal treatment protocol for a delayed infection from an immune-evading, coated virus. We derive a system of partial differential equations to model the interaction between a growing tumour and this coated oncolytic virus. Using this system, we show that viruses with inhibited viral clearance and infectivity are more effective than uncoated viruses. We then consider a hierarchical level of coating that degrades over time and determine a nontrivial initial distribution of coating levels needed to produce the lowest tumour volume. Interestingly, we find that a bimodal mixture of thickly coated and thinly coated virus is necessary to achieve a minimum tumour size. Throughout this article we also consider the effects of immune clearance of the virus. We show how different immune responses instigate significantly different treatment outcomes.

References

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