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利用CAR-T细胞技术过继治疗胶质母细胞瘤的标准治疗方案

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发表于 2016-1-26 11:11:42 | 显示全部楼层 |阅读模式
Generation of CAR T cells for adoptive therapy in the context of glioblastoma standard of care.


Adoptive T cell immunotherapy offers a promising strategy for specifically targeting and eliminating malignant gliomas. T cells can be engineered ex vivo to express chimeric antigen receptors specific for glioma antigens (CAR T cells). The expansion and function of adoptively transferred CAR T cells can be potentiated by the lymphodepletive and tumoricidal effects of standard of care chemotherapy and radiotherapy. We describe a method for generating CAR T cells targeting EGFRvIII, a glioma-specific antigen, and evaluating their efficacy when combined with a murine model of glioblastoma standard of care. T cells are engineered by transduction with a retroviral vector containing the anti-EGFRvIII CAR gene. Tumor-bearing animals are subjected to host conditioning by a course of temozolomide and whole brain irradiation at dose regimens designed to model clinical standard of care. CAR T cells are then delivered intravenously to primed hosts. This method can be used to evaluate the antitumor efficacy of CAR T cells in the context of standard of care.

利用CAR-T细胞技术过继治疗胶质母细胞瘤的标准治疗方案

过继T细胞的免疫治疗为特异性靶向治疗和消灭恶性脑胶质瘤提供了一个非常有前途的治疗方案。T细胞能够在体外加工并表达靶向胶质母细胞瘤抗原的嵌合抗原受体。过继性T细胞的增殖和功能能够通过lymphodepletive和标准的放化疗带来的肿瘤杀伤能力得到提高。我们描述了一种生产靶向EGFRvIII(一种胶质母细胞瘤表面抗原)的CAR-T细胞,评估其在标准护理下的胶质母细胞瘤小鼠模型中的作用效果。通过一个包含靶向EGFRvIII的CAR基因的慢病毒载体转导来加工T细胞。肿瘤动物模型使用一系列替莫唑胺以及使用临床级别剂量的全脑射线治疗,而后使用CAR-T细胞静脉注射入动物模型体内,这种方法可以用来评估标准护理下,CAR-T细胞技术的抗肿瘤能力。
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