Ruiz-Ramírez Javier, Ziemys Arturas, Dogra Prashant, Ferrari Mauro
Mathematics in Medicine Program, The Houston Methodist Research Institute, HMRI R8-122, 6670 Bertner Ave., Houston, TX 77030 USA.
Mathematics in Medicine Program, The Houston Methodist Research Institute, HMRI R8-122, 6670 Bertner Ave., Houston, TX 77030 USA.
J Theor Biol. 2020 May 21;493:110193. doi: 10.1016/j.jtbi.2020.110193. Epub 2020 Feb 28.
We present a physiologically-based pharmacokinetic modeling platform capable of simulating the biodistribution of different therapeutic agents, including cells, their interactions within the immune system, redistribution across lymphoid compartments, and infiltration into tumor tissues. This transport-based platform comprises a distinctive implementation of a tumor compartment with spatial heterogeneity which enables the modeling of tumors of different size, necrotic state, and agent infiltration capacity. We provide three validating and three exploratory examples that illustrate the capabilities of the proposed approach. The results show that the model can recapitulate immune cell balance across different compartments, respond to antigen stimulation, simulate immune vaccine effects, and immune cell infiltration to tumors. Based on the results, the model can be used to study problems pertinent to current immunotherapies and has the potential to assist medical techniques that rely on the transport of biological species.
我们提出了一个基于生理学的药代动力学建模平台,该平台能够模拟不同治疗剂的生物分布,包括细胞、它们在免疫系统内的相互作用、在淋巴区室之间的重新分布以及向肿瘤组织的浸润。这个基于转运的平台包括一个具有空间异质性的肿瘤区室的独特实现方式,这使得能够对不同大小、坏死状态和药剂浸润能力的肿瘤进行建模。我们提供了三个验证性示例和三个探索性示例来说明所提出方法的能力。结果表明,该模型可以概括不同区室间的免疫细胞平衡、对抗原刺激作出反应、模拟免疫疫苗效果以及免疫细胞向肿瘤的浸润。基于这些结果,该模型可用于研究与当前免疫疗法相关的问题,并有可能辅助依赖生物物种转运的医学技术。