Mathematical Model for Radial Expansion and Conflation of Intratumoral Infectious Centers Predicts Curative Oncolytic Virotherapy Parameters
Mathematical Model for Radial Expansion and Conflation of Intratumoral Infectious Centers Predicts Curative Oncolytic Virotherapy Parameters
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DOI：
10.1371/journal.pone.0073759
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发表时间：
2013-09-11
期刊：
影响因子：
3.7
通讯作者：
Russell, Stephen J.
中科院分区：
文献类型：
--
作者：
Bailey, Kent;Kirk, Amber;Russell, Stephen J.
需要简单、归纳的溶瘤病毒治疗数学模型来指导方案设计和改善治疗结果。对骨髓瘤动物模型单次静脉注射溶瘤性水泡性口炎病毒后消退的浆细胞瘤的分析显示，瘤内病毒的传播受到空间限制，几乎完全通过随机分布的感染中心的径向扩张发生。从这些实验观察中，我们开发了一个简单的模型来计算治疗肿瘤内任何细胞的存活概率。该模型预测，初始感染细胞的密度或感染中心的平均最大半径的微小变化将对治疗结果产生重大影响，这一点在实验中得到了证实。该模型为优化病毒治疗方案提供了一种实用而灵活的工具。
Simple, inductive mathematical models of oncolytic virotherapy are needed to guide protocol design and improve treatment outcomes. Analysis of plasmacytomas regressing after a single intravenous dose of oncolytic vesicular stomatitis virus in myeloma animal models revealed that intratumoral virus spread was spatially constrained, occurring almost exclusively through radial expansion of randomly distributed infectious centers. From these experimental observations we developed a simple model to calculate the probability of survival for any cell within a treated tumor. The model predicted that small changes to the density of initially infected cells or to the average maximum radius of infected centers would have a major impact on treatment outcome, and this was confirmed experimentally. The new model provides a useful and flexible tool for virotherapy protocol optimization.