School of Mathematics and Statistics, The University of Sydney, Sydney, NSW, 2006, Australia.
Department of Bioengineering, Hanyang University, 17 Haengdang-Dong, Seongdong-Gu, Seoul, Korea.
Bull Math Biol. 2018 Jun;80(6):1615-1629. doi: 10.1007/s11538-018-0424-4. Epub 2018 Apr 11.
Oncolytic virotherapy is an experimental cancer treatment that uses genetically engineered viruses to target and kill cancer cells. One major limitation of this treatment is that virus particles are rapidly cleared by the immune system, preventing them from arriving at the tumour site. To improve virus survival and infectivity Kim et al. (Biomaterials 32(9):2314-2326, 2011) modified virus particles with the polymer polyethylene glycol (PEG) and the monoclonal antibody herceptin. Whilst PEG modification appeared to improve plasma retention and initial infectivity, it also increased the virus particle arrival time. We derive a mathematical model that describes the interaction between tumour cells and an oncolytic virus. We tune our model to represent the experimental data by Kim et al. (2011) and obtain optimised parameters. Our model provides a platform from which predictions may be made about the response of cancer growth to other treatment protocols beyond those in the experiments. Through model simulations, we find that the treatment protocol affects the outcome dramatically. We quantify the effects of dosage strategy as a function of tumour cell replication and tumour carrying capacity on the outcome of oncolytic virotherapy as a treatment. The relative significance of the modification of the virus and the crucial role it plays in optimising treatment efficacy are explored.
溶瘤病毒治疗是一种利用基因工程病毒靶向和杀死癌细胞的实验性癌症治疗方法。这种治疗方法的一个主要限制是病毒颗粒会被免疫系统迅速清除,从而阻止它们到达肿瘤部位。为了提高病毒的存活率和感染力,Kim 等人(Biomaterials 32(9):2314-2326, 2011)用聚合物聚乙二醇(PEG)和单克隆抗体赫赛汀对病毒颗粒进行了修饰。虽然 PEG 修饰似乎提高了血浆保留和初始感染力,但也增加了病毒颗粒到达时间。我们推导了一个描述肿瘤细胞与溶瘤病毒相互作用的数学模型。我们通过调整模型来代表 Kim 等人(2011)的实验数据,并获得了优化的参数。我们的模型为预测癌症生长对实验之外的其他治疗方案的反应提供了一个平台。通过模型模拟,我们发现治疗方案会对结果产生巨大影响。我们将剂量策略的效果作为肿瘤细胞复制和肿瘤承载能力的函数进行量化,以评估其对溶瘤病毒治疗效果的影响。还探讨了病毒修饰的相对重要性及其在优化治疗效果方面的关键作用。