Lee Taeyong, Jenner Adrianne L, Kim Peter S, Lee Jeehyun
Department of Mathematics, College of Science, Yonsei University, Seoul, Korea.
Département de mathématiques et de statistique, Université de Montréal, Montréal, Canada.
Math Biosci Eng. 2020 Feb 12;17(3):2361-2383. doi: 10.3934/mbe.2020126.
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.
溶瘤病毒疗法是一种很有前景的癌症治疗方法，它利用病毒的力量。通过基因工程，这些病毒被培养以感染和破坏癌细胞。虽然这种疗法在一系列临床试验中已显示出成效，但该领域一个尚未解决的问题是确定对这些病毒更有效的干扰方法。在这项工作中，我们采用一种可控疗法来确定针对一种免疫逃逸包膜病毒延迟感染的最佳治疗方案。我们推导了一个偏微分方程组来模拟生长中的肿瘤与这种包膜溶瘤病毒之间的相互作用。利用这个系统，我们表明病毒清除和感染性受到抑制的病毒比无包膜病毒更有效。然后，我们考虑随着时间推移会降解的分层包膜，并确定产生最小肿瘤体积所需的包膜水平的非平凡初始分布。有趣的是，我们发现需要厚包膜病毒和薄包膜病毒的双峰混合物才能实现最小肿瘤尺寸。在整篇文章中，我们还考虑了病毒免疫清除的影响。我们展示了不同的免疫反应如何引发显著不同的治疗结果。
