论文标题
考虑多个CAR T细胞结合的神经胶质瘤细胞和T细胞的相互作用
Modeling interaction of Glioma cells and CAR T-cells considering multiple CAR T-cells bindings
论文作者
论文摘要
嵌合抗原受体（CAR）基于T细胞的免疫疗法表明其在治疗血液癌中的潜力，目前正在广泛研究其对实体瘤的应用。对于神经胶质瘤脑肿瘤，各种汽车T细胞靶标包括IL13RA2，EGFRVIII，HER2，EPHA2，GD2，B7-H3和氯托毒素。在这项工作中，我们有兴趣开发靶向用于治疗神经胶质瘤的汽车T细胞的IL13RA2的数学模型。我们专注于扩展Kuznetsov等人的工作。 （1994）考虑了多个CAR T细胞与单个神经胶质瘤细胞的结合以及这些多细胞结合物的动力学。与不考虑细胞结合的模型相比，我们的模型更准确地描述了实验观察到的CAR T细胞杀死测定数据。此外，我们得出了决定治疗成功或失败的CAR T细胞膨胀率的条件。最后，我们表明我们的模型在患者来源的脑肿瘤细胞中捕获了在低，中和高抗原受体密度下的不同汽车T细胞杀死动力学。
Chimeric antigen receptor (CAR) T-cell based immunotherapy has shown its potential in treating blood cancers, and its application to solid tumors is currently being extensively investigated. For glioma brain tumors, various CAR T-cell targets include IL13Ra2, EGFRvIII, HER2, EphA2, GD2, B7-H3, and chlorotoxin. In this work, we are interested in developing a mathematical model of IL13Ra2 targeting CAR T-cells for treating glioma. We focus on extending the work of Kuznetsov et al. (1994) by considering binding of multiple CAR T-cells to a single glioma cell, and the dynamics of these multi-cellular conjugates. Our model more accurately describes experimentally observed CAR T-cell killing assay data than a model which does not consider cell binding. Moreover, we derive conditions in the CAR T-cell expansion rate that determines treatment success or failure. Finally, we show that our model captures distinct CAR T-cell killing dynamics at low, medium, and high antigen receptor densities in patient-derived brain tumor cells.
