Jacobsen Karly, Russell Luke, Kaur Balveen, Friedman Avner
Mathematical Biosciences Institute, The Ohio State University, Columbus, OH, 43210, USA,
Bull Math Biol. 2015 Jun;77(6):984-1012. doi: 10.1007/s11538-015-0074-8. Epub 2015 Mar 11.
Oncolytic virus (OV) is a genetically engineered virus that can selectively replicate in and kill tumor cells while not harming normal cells. OV therapy has been explored as a treatment for numerous cancers including glioblastoma, an aggressive and devastating brain tumor. Experiments show that extracellular matrix protein CCN1 limits OV therapy of glioma by orchestrating an antiviral response and enhancing the proinflammatory activation and migration of macrophages. Neutralizing CCN1 by antibody has been demonstrated to improve OV spread and tends to increase the time to disease progression. In this paper, we develop a mathematical model to investigate the effects of CCN1 on the treatment of glioma with oncolytic herpes simplex virus. We show that numerical simulations of the model are in agreement with the experimental results and then use the model to explore the anti-tumor effects of combining antibodies with OV therapy. Model simulations suggest that the macrophage content of the tumor is a critical factor to the success of OV therapy and to the reduction in tumor volume gained with the CCN1 antibody.
溶瘤病毒（OV）是一种经过基因工程改造的病毒，它能够在肿瘤细胞中选择性复制并杀死肿瘤细胞，同时不损害正常细胞。溶瘤病毒疗法已被探索用于治疗多种癌症，包括胶质母细胞瘤，这是一种侵袭性且具有破坏性的脑肿瘤。实验表明，细胞外基质蛋白CCN1通过协调抗病毒反应以及增强巨噬细胞的促炎激活和迁移来限制胶质瘤的溶瘤病毒疗法。已证明用抗体中和CCN1可改善溶瘤病毒的扩散，并倾向于延长疾病进展时间。在本文中，我们建立了一个数学模型来研究CCN1对单纯疱疹病毒溶瘤治疗胶质瘤的影响。我们表明该模型的数值模拟与实验结果一致，然后使用该模型探索抗体与溶瘤病毒疗法联合使用的抗肿瘤效果。模型模拟表明，肿瘤中的巨噬细胞含量是溶瘤病毒疗法成功以及使用CCN1抗体使肿瘤体积缩小的关键因素。
