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表达可切换的仿制Fc受体CD64的T淋巴细胞表现出增强的持久性和抗瘤活性

Yuanbin Cui¹, Tingjie Yuan², Ying Wang³

¹China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

|July 12, 2023

概括

一种新型的模拟性Fc受体CD64 (CFR64) 增强了模拟性抗原受体 (CAR) T细胞治疗固体瘤的功效. 与传统的CAR T细胞相比,CFR64 T细胞表现出更好的,持久的抗癌活性和降低的毒性.

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细胞疗法在治疗固体瘤方面表现出局限性,原因是其持续性不足以及瘤点和瘤外毒性.
开发先进的CAR T细胞策略对于提高癌症治疗的有效性和安全性至关重要.

研究的目的:

设计和评估一种新型的抗体引导可切换的CAR载体,即嵌合式Fc受体CD64 (CFR64),用于加强T细胞治疗固体瘤.
为了比较CFR64 T细胞与传统的CAR T细胞的抗瘤疗效,持久性和安全性.

主要方法:

产生了表达CFR64,高亲和度CD16变体 (CD16v) 或CD32A的工程T细胞.
用癌细胞系进行了细胞毒性测试.
分析了长期细胞毒性,T细胞耗尽标志物,免疫突触稳定性,下游信号和线粒体形态.

主要成果:

与表达CD16v或CD32A的T细胞相比,CFR64T细胞对癌细胞表现出更高的细胞毒性.
CFR64 T细胞表现出增强的长期细胞毒性和对T细胞耗尽的抵抗力.
与传统的CAR T细胞不同,CFR64 T细胞形成了更稳定的免疫突触,信号强度较低,并在刺激时显示了融合的线粒体.

结论:

CFR64代表了一种有希望的可控制的工程T细胞疗法,用于固体瘤.
CFR64 T细胞提供长时间的持久性和持续的抗瘤活性,可能克服当前CAR T细胞疗法的局限性.

关键词:

在CAR T细胞中.这是一个CD64CD64CD64CD.CP: 癌症癌症癌症 CP: 免疫学免疫学这是一个Fc受体.免疫学的突触.线粒体融合是指线粒体的融合.这就是特拉斯图祖马布 (trastuzumab).

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