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肿瘤溶瘤病毒在异质细胞群体中的时空传播。

Spatiotemporal spread of oncolytic virus in a heterogeneous cell population.

机构信息

Institute of Physics, Universitat Kassel, Kassel, Germany; Department of Physics & Astronomy, Texas Christian University, Fort Worth, TX, USA.

Department of Physics & Astronomy, Texas Christian University, Fort Worth, TX, USA.

出版信息

Comput Biol Med. 2024 Dec;183:109235. doi: 10.1016/j.compbiomed.2024.109235. Epub 2024 Oct 5.

Abstract

Oncolytic (cancer-killing) virus treatment is a promising new therapy for cancer, with many viruses currently being tested for their ability to eradicate tumors. One of the major stumbling blocks to the development of this treatment modality has been preventing spread of the virus to non-cancerous cells. Our recent ability to manipulate RNA and DNA now allows for the possibility of creating designer viruses specifically targeted to cancer cells, thereby significantly reducing unwanted side effects in patients. In this study, we use a partial differential equation model to determine the characteristics of a virus needed to contain spread of an oncolytic virus within a spherical tumor and prevent it from spreading to non-cancerous cells outside the tumor. We find that oncolytic viruses that have different infection rates or different cell death rates in cancer and non-cancerous cells can be made to stay within the tumor. We find that there is a minimum difference in infection rates or cell death rates that will contain the virus and that this threshold value depends on the growth rate of the cancer. Identification of these types of thresholds can help researchers develop safer strains of oncolytic viruses allowing further development of this promising treatment.

摘要

溶瘤(杀癌)病毒治疗是一种有前途的癌症新疗法,目前有许多病毒正在测试其消灭肿瘤的能力。这种治疗方法发展的主要障碍之一是防止病毒传播到非癌细胞。我们最近操纵 RNA 和 DNA 的能力现在使得有可能创建专门针对癌细胞的设计病毒,从而显著减少患者的不良反应。在这项研究中,我们使用偏微分方程模型来确定在球形肿瘤内控制溶瘤病毒传播并防止其传播到肿瘤外的非癌细胞所需的病毒特性。我们发现,在癌症和非癌细胞中具有不同感染率或不同细胞死亡率的溶瘤病毒可以被限制在肿瘤内。我们发现,存在一个将病毒包含在内的最小感染率或细胞死亡率差异,并且该阈值值取决于癌症的增长率。识别这些类型的阈值可以帮助研究人员开发更安全的溶瘤病毒株,从而进一步开发这种有前途的治疗方法。

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