肿瘤细胞治疗研究
英文原题：Modeling interaction of Glioma cells and CAR T-cells considering multiple CAR T-cells bindings.
基于嵌合抗原受体（CAR）T 细胞的免疫治疗已显示出治疗血液肿瘤的潜力，其在实体瘤中的应用目前正被广泛研究。
基于嵌合抗原受体（CAR）T 细胞的免疫疗法已显示出治疗血液系统肿瘤的潜力，目前正在广泛研究其在实体瘤中的应用。胶质瘤脑肿瘤的 CAR T 细胞靶点包括 IL13Rα2、EGFRvIII、HER2、EphA2、GD2、B7-H3 和绿脓杆菌外毒素相关的绿脓杆菌毒素受体 chlorotoxin。本研究旨在建立靶向 IL13Rα2 的 CAR T 细胞治疗胶质瘤的数学模型。我们在 Kuznetsov 等人（1994）的工作基础上，考虑多个 CAR T 细胞与单个胶质瘤细胞结合及此类多细胞结合体的动力学。与未考虑多细胞结合体的模型相比，我们的模型更准确地描述了实验观察到的 CAR T 细胞杀伤试验数据。此外，我们推导出决定治疗成功或失败的 CAR T 细胞扩增率条件。最后，我们显示该模型可捕捉患者来源脑肿瘤细胞中从低到高抗原受体密度下不同的 CAR T 细胞杀伤动力学。
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 IL13R 2, EGFRvIII, HER2, EphA2, GD2, B7-H3, and chlorotoxin. In this work, we are interested in developing a mathematical model of IL13R 2 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 the models which do not consider multi-cellular conjugates. 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 from low to high antigen receptor densities in patient-derived brain tumor cells.
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