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针对HER2的人性化单域抗体增强了仿真抗原受体T细胞的功能

Rui Zheng¹, Yuankun Chen², Yiting Zhang¹

¹State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi, China.

Frontiers in immunology

|November 29, 2023

概括

使用人性化scFvs降低仿真抗原受体 (CAR) 亲和力,保持抗瘤疗效,同时提高CAR-T细胞治疗安全性. 较低亲和度的CAR-T细胞表现出增强的持久性和减少的细胞因子释放,以更好地消除瘤.

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 (CARs) 将T细胞重定向对抗瘤.
CAR组分的亲和力影响T细胞的功能和疗效.
优化CAR亲和力对于增强CAR-T细胞治疗至关重要.

研究的目的:

为了研究降低CAR亲和力对CAR-T细胞功能的影响.
为了评估人性化的CARs的安全性和有效性,具有不同的亲和力.
探索较低亲和度CARs在改善癌症免疫疗法的潜力.

主要方法:

使用不同亲和度的人性化抗HER2抗体构建的CAR-T细胞.
使用基于光链可变域 (VL) 的CAR-T细胞.
在体外和体内评估了抗瘤疗效,持久性和细胞因子水平.

主要成果:

适度降低的CAR亲和力 (基于VL的CAR-T) 维持了抗瘤疗效.
与高亲和度的CAR-T细胞相比,较低亲和度的CAR-T细胞显示出更好的安全性.
基于VL的CAR-T细胞表现出长期持续的瘤消除,增强的持久性和更低的体内细胞因子水平.

结论:

降低CAR亲和力为CAR-T细胞优化提供了一个可行的策略.
较低亲和度的CAR可以提高CAR-T细胞治疗的安全性.
这种方法有可能扩大CAR T细胞在癌症治疗中的应用.

关键词:

在HER2中,HER2是HER2.在T细胞工程方面,T细胞工程收养免疫疗法采用免疫疗法.抗原结合域是一个抗原结合域.仿制性抗原受体的仿制性抗原受体

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