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自发的TIGIT阻断scFv增强了固体瘤中的CAR-T免疫疗法

Fan Yang¹, Fan Zhang¹, Feng Ji¹

¹Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.

Frontiers in immunology

|June 26, 2023

概括

阻断TIGIT免疫检查点可以增强化学抗原受体T细胞 (CAR-T) 治疗对固体瘤的疗效. 这种策略通过克服瘤微环境来改善CAR-T细胞活性和瘤回归.

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T细胞 (CAR-T) 疗法对癌症治疗具有前景,但由于复杂的瘤微环境和免疫检查点,在固体瘤中面临挑战.
TIGIT作为一个免疫检查点,通过结合瘤细胞的CD155来抑制T细胞介导的瘤细胞杀死.

研究的目的:

研究阻断TIGIT/CD155相互作用的疗效,以增强固体瘤的CAR-T细胞治疗.
评估抗美索林 (MSLN) CAR-T细胞与TIGIT阻断的组合,以改善抗瘤作用.

主要方法:

产生抗MSLN的CAR-T细胞,并与抗TIGIT疗法结合.
用CAR-T细胞进行基因工程,以构成性地产生阻断TIGIT的单链可变片段 (scFvs).
在体外评估细胞杀死和细胞因子释放,在体内评估瘤回归和CAR-T细胞透/激活.

主要成果:

抗TIGIT疗法在体外显著增强了抗MSLN CAR-T细胞对细胞的细胞毒性活性.
具有TIGIT阻断scFvs的工程CAR-T细胞显示细胞因子释放增加和瘤细胞杀死增加.
在体内研究表明,瘤回归得到改善,CAR-T细胞透得到增强,并在瘤微环境中激活.

结论:

阻止TIGIT免疫检查点是一种可行的策略,可以提高CAR-T细胞治疗在固体瘤中的抗瘤疗效.
将CAR-T细胞疗法与TIGIT阻断相结合,特别是通过工程CAR-T细胞,为固体瘤治疗提供了一个有前途的治疗方法.

关键词:

在CAR-T细胞中.在MSLN中使用.这是一个紧张的紧张.免疫疗法免疫疗法固体瘤是一种固体瘤.

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