A Mathematical Model for On-Target Off-Tumor Effect of CAR-T Cells on Gliomas

Daniela S. Santurio, L. Barros
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引用次数: 2

Abstract

CAR-T cell immunotherapy involves genetically reprogrammed T-lymphocytes that interact with cancer cells and activate an anti-tumor immune response. This therapy has been approved for clinical use for hematological cancers, but new challenges have emerged in the treatment of solid tumors. Some of the challenges include the heterogeneity of antigen expression found in solid tumors, including antigen-positive non-tumoral cells, the immune inhibitory molecule expression, and CAR-T cell trafficking difficulty within the tumor microenvironment. We proposed a mathematical model to describe the “on-target” and “off-tumor” effects of CAR-T cell therapy on gliomas, and we investigated which parameters influenced the final outcome using a global sensitivity analysis. Our model highlights the dynamics of CAR-T cell therapy, tumor, and healthy populations (antigen-positive glia, antigen-negative glia, and neurons), and it provides novel insight into the consequences of “on-target” “off-tumor” effects, particularly in the neuronal loss.
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CAR-T细胞对胶质瘤靶向脱靶作用的数学模型
CAR-T细胞免疫疗法涉及基因重编程的T淋巴细胞,它们与癌症细胞相互作用并激活抗肿瘤免疫反应。这种疗法已被批准用于血液系统癌症的临床治疗,但在实体瘤的治疗中出现了新的挑战。一些挑战包括在实体瘤中发现的抗原表达的异质性,包括抗原阳性的非肿瘤细胞、免疫抑制分子表达,以及肿瘤微环境中CAR-T细胞运输的困难。我们提出了一个数学模型来描述CAR-T细胞治疗胶质瘤的“靶向”和“离瘤”效应,并使用全局敏感性分析研究了哪些参数影响最终结果。我们的模型强调了CAR-T细胞治疗、肿瘤和健康人群(抗原阳性神经胶质细胞、抗原阴性神经胶质细胞和神经元)的动态,并为“靶向”“肿瘤外”效应的后果,特别是神经元损失提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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