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通过计算机设计的高亲和蛋白质结合剂,通过CAR T细胞向质母细胞中过度表达的抗原

Zhen Xia^1,2,3,4,5, Qihan Jin^1,2,5,6, Zhilin Long^1,2,3,4,5

¹Westlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.

Nature biomedical engineering

|October 17, 2024

概括

使用新设计的蛋白质结合剂向质母细胞瘤 (GBM) 的新CAR T细胞疗法显示出改善的抗瘤活性. 这些工程T细胞表现出增强的增殖,细胞因子分泌和抗疲劳能力,表现优于传统的CAR T细胞.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物技术是生物技术.

背景情况:

化学抗原受体 (CAR) T细胞疗法在质母细胞瘤 (GBM) 中显示出有限的疗效.
现有的CAR结构经常使用抗体衍生的单链可变片段 (scFvs) 作为抗原结合域.
质母细胞瘤过度表达了表皮生长因子受体 (EGFR) 和CD276.6等点.

研究的目的:

为GBM治疗开发具有新设计的蛋白质结合剂的新型CAR T细胞.
与基于scFv的CAR T细胞相比,评估这些工程CAR T细胞的治疗性能.

主要方法:

经过计算设计的新型蛋白质结合剂,对EGFR和CD276.有很高的亲和力.
使用这些新型结合剂生成CAR T细胞.
在体外和体内评估CAR T细胞增殖,细胞因子分泌,抗疲劳性和抗瘤活性.
批量和单细胞转录特征分析,以分析CAR表达和稳定性.

主要成果:

新设计的结合剂增强了CAR T细胞的增殖,细胞毒性细胞因子分泌和抵抗细胞耗尽.
改造的CAR T细胞在体外和体内表现出更好的抗瘤疗效.
设计结合剂的CAR显示出更高的表面表达和更高的降解耐受性.

结论:

蛋白质结合剂的新设计提供了一种有希望的策略,以增强对质母细胞瘤的CAR T细胞疗法.
这种方法可以提高其他固体瘤的CAR T细胞疗法的疗效.
工程结合剂在CAR T细胞设计中比传统的scFv领域具有潜在的进步.

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