Mathematical modelling of a hypoxia-regulated oncolytic virus delivered by tumour-associated macrophages.
Mathematical modelling of a hypoxia-regulated oncolytic virus delivered by tumour-associated macrophages.
复制标题
通过肿瘤相关巨噬细胞传递的缺氧调节病毒的数学模型。
DOI：
10.1016/j.jtbi.2018.10.044
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发表时间：
2019-01-14
影响因子：
2
通讯作者：
Byrne HM
中科院分区：
文献类型：
--
作者：
Boemo MA;Byrne HM
巨噬细胞在肿瘤球体内释放溶瘤病毒的连续体模型。该治疗联合放疗的预测模型。探讨放疗和溶瘤病毒治疗的时间安排。肿瘤缺氧长期以来一直是癌症治疗的一个挑战：缺氧区域的血管化不良阻碍了化疗药物的输送和对放疗的反应，并且在治疗结束后存活下来的缺氧癌细胞可以触发肿瘤再生。肿瘤相关巨噬细胞是很有吸引力的药物递送载体，因为它们定位于肿瘤的缺氧区域。在本文中，我们推导了一个数学模型，用于巨噬细胞浸润体外肿瘤球体，巨噬细胞在缺氧条件下释放溶瘤腺病毒。我们使用这个模型来预测放疗和工程巨噬细胞联合使用的治疗方案的疗效。我们的工作表明，工程巨噬细胞应该在放疗后立即引入，以获得最大的治疗效果。我们的模型提供了一个框架，可以指导未来的实验，以确定如何协调多轮放疗和巨噬细胞病毒治疗，以最大限度地提高治疗反应。
A continuum model of macrophages releasing an oncolytic virus within a tumour spheroid. Predictive modelling of this treatment given in combination with radiotherapy. Investigation into how radiotherapy and oncolytic virotherapy should be scheduled. Tumour hypoxia has long presented a challenge for cancer therapy: Poor vascularisation in hypoxic regions hinders both the delivery of chemotherapeutic agents and the response to radiotherapy, and hypoxic cancer cells that survive treatment can trigger tumour regrowth after treatment has ended. Tumour-associated macrophages are attractive vehicles for drug delivery because they localise in hypoxic areas of the tumour. In this paper, we derive a mathematical model for the infiltration of an in vitro tumour spheroid by macrophages that have been engineered to release an oncolytic adenovirus under hypoxic conditions. We use this model to predict the efficacy of treatment schedules in which radiotherapy and the engineered macrophages are given in combination. Our work suggests that engineered macrophages should be introduced immediately after radiotherapy for maximum treatment efficacy. Our model provides a framework that may guide future experiments to determine how multiple rounds of radiotherapy and macrophage virotherapy should be coordinated to maximise therapeutic responses.
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