Pooladvand Pantea, Yun Chae-Ok, Yoon A-Rum, Kim Peter S, Frascoli Federico
School of Mathematics and Statistics, The University of Sydney, Sydney, NSW 2006, Australia.
Department of Bioengineering, Collage of Engineering, Hanyang University, Seoul, South Korea; Institute of Nano Science and Technology (INST), Hanyang University, Seoul, South Korea.
Math Biosci. 2021 Apr;334:108520. doi: 10.1016/j.mbs.2020.108520. Epub 2020 Dec 5.
A model capturing the dynamics between virus and tumour cells in the context of oncolytic virotherapy is presented and analysed. The ability of the virus to be internalised by uninfected cells is described by an infectivity parameter, which is inferred from available experimental data. The parameter is also able to describe the effects of changes in the tumour environment that affect viral uptake from tumour cells. Results show that when a virus is inoculated inside a growing tumour, strategies for enhancing infectivity do not lead to a complete eradication of the tumour. Within typical times of experiments and treatments, we observe the onset of oscillations, which always prevent a full destruction of the tumour mass. These findings are in good agreement with available laboratory results. Further analysis shows why a fully successful therapy cannot exist for the proposed model and that care must be taken when designing and engineering viral vectors with enhanced features. In particular, bifurcation analysis reveals that creating longer lasting virus particles or using strategies for reducing infected cell lifespan can cause unexpected and unwanted surges in the overall tumour load over time. Our findings suggest that virotherapy alone seems unlikely to be effective in clinical settings unless adjuvant strategies are included.
本文提出并分析了一个在溶瘤病毒疗法背景下捕捉病毒与肿瘤细胞之间动态关系的模型。未感染细胞摄取病毒的能力由一个感染性参数描述，该参数是根据现有实验数据推断得出的。该参数还能够描述肿瘤环境变化对病毒从肿瘤细胞摄取的影响。结果表明，当在生长的肿瘤内部接种病毒时，增强感染性的策略并不能导致肿瘤的完全根除。在实验和治疗的典型时间内，我们观察到振荡的出现，这总是阻止肿瘤块的完全破坏。这些发现与现有的实验室结果高度一致。进一步分析表明了为什么对于所提出的模型不存在完全成功的治疗方法，以及在设计和构建具有增强特性的病毒载体时必须谨慎。特别是，分岔分析表明，创造更持久的病毒颗粒或使用减少受感染细胞寿命的策略可能会随着时间的推移导致总体肿瘤负荷出现意想不到的、不必要的激增。我们的研究结果表明，除非纳入辅助策略，单纯的病毒疗法在临床环境中似乎不太可能有效。
