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The role of viral infectivity in oncolytic virotherapy outcomes: A mathematical study
Mathematical Biosciences ( IF 1.9 ) Pub Date : 2020-12-05 , DOI: 10.1016/j.mbs.2020.108520
Pantea Pooladvand 1 , Chae-Ok Yun 2 , A-Rum Yoon 2 , Peter S Kim 1 , Federico Frascoli 3
Affiliation  

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.



中文翻译:

病毒感染性在溶瘤病毒治疗结果中的作用:一项数学研究

提出并分析了在溶瘤病毒疗法的背景下捕获病毒和肿瘤细胞之间动态的模型。病毒被未感染细胞内化的能力由感染性参数描述,该参数是从可用的实验数据推断出来的。该参数还能够描述影响肿瘤细胞病毒摄取的肿瘤环境变化的影响。

结果表明,当病毒被接种到正在生长的肿瘤内时,增强传染性的策略并不能完全根除肿瘤。在实验和治疗的典型时间内,我们观察到振荡的开始,这总是防止肿瘤块的完全破坏。这些发现与可用的实验室结果非常一致。

进一步的分析表明,为什么所提出的模型不能存在完全成功的疗法,并且在设计和改造具有增强功能的病毒载体时必须小心。特别是,分叉分析表明,随着时间的推移,产生更持久的病毒颗粒或使用减少受感染细胞寿命的策略会导致整体肿瘤负荷出现意外和不必要的激增。我们的研究结果表明,除非包括辅助策略,否则单独的病毒疗法似乎不太可能在临床环境中有效。

更新日期:2020-12-05
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