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改造的CD47保护T细胞以增强抗瘤免疫力

Sean A Yamada-Hunter^1,2, Johanna Theruvath¹, Brianna J McIntosh³

¹Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.

|May 15, 2024

概括

结合抗CD47抗体和T细胞治疗可以消除癌细胞,但也可以清除T细胞. 使用CD47变异的T细胞可以防止这种清除,从而增强抗瘤功效.

科学领域:

免疫学
癌症学
生物技术

背景情况:

通过采用转移的T细胞和CD47-SIRPα轴阻断剂是有前途的癌症免疫疗法.
结合这些方法旨在增强抗瘤功效,但在T细胞清除方面面临挑战.

研究的目的:

在与抗CD47抗体结合时,研究工程T细胞的快速巨介导清除的挑战.
开发一种策略,以克服这种清除并提高结合T细胞和巨细胞的癌症治疗效果.

主要方法:

采用转移T细胞 (CAR T或TCR T) 进行的抗CD47抗体.
工程T细胞表达抗CD47抗体介导清除的CD47变体 (47E).
在体内评估T细胞持久性,巨细胞招募和抗瘤功效.

主要成果:

抗CD47抗体导致标准CAR T细胞的快速清除,作为安全开关.
在抗CD47抗体治疗后,表达CD47变体 (47E) 的T细胞抵抗了巨细胞的清除.
与47E表达性T细胞的联合治疗增强了巨细胞的招募,并显示出协同作用的抗瘤疗效.

结论:

在联合免疫疗法中,巨细胞是T细胞持久性的关键调节者.
工程 CD47 变种可以克服抗 CD47 抗体介导的 T 细胞枯竭.
这种方法提供了一种策略,可以同时利用T细胞和巨细胞的抗瘤活性来加强固体瘤治疗.

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