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通过条形码蛋白质域组合聚合查提炼仿真抗原受体

Xavier Rios¹, Osmay Pardias², Marc A Morales²

¹Center for Advanced Innate Cell Therapy, Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.

Molecular therapy : the journal of the American Society of Gene Therapy

|September 14, 2023

概括

研究人员开发了一种新的克隆策略,快速创建和测试许多化学抗原受体 (CAR) -T细胞设计. 这种方法确定了具有改善体内抗瘤活性的新型CAR架构,加速了癌症免疫治疗的发展.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
生物技术是生物技术.

背景情况:

化学抗原受体 (CAR) -T细胞疗法是一种有前途的癌症免疫治疗方法.
目前开发新型CAR构造的方法效率低下,耗时.
需要加速方法来评估和比较CAR设计.

研究的目的:

开发一种新的克隆策略,以高效地生成和评估CAR结构.
确定最佳的CAR架构,以增强T细胞的增殖和扩张.
发现具有卓越的体内抗瘤活性的新型CAR设计.

主要方法:

一种新的克隆策略,使用通过粗结合 (blunt ligation) 进行CAR域的顺序组装.
每个CAR域都被分配了一个独特的DNA条形码用于量化.
产生360个CAR构造,针对CD19和GD2瘤抗原.
使用下一代测序来量化条形码频率并评估CAR功能.

主要成果:

选确定了链域在CAR功能中的关键作用.
CD8a和IgG4链表明,根据目标抗原 (CD19和GD2) 对CAR性能产生相反的影响.
与FDA批准的治疗相比,两种具有IgG4链的新型CD19-CAR架构在体内显示出优异的抗瘤活性.

结论:

开发的克隆策略显著加快了CAR设计的评估和比较.
这种方法可以快速识别用于癌症免疫治疗的高性能CAR结构.
这些发现为快速开发下一代CAR-T细胞疗法铺平了道路.

关键词:

癌症免疫疗法免疫疗法细胞治疗疗法细胞治疗疗法嵌合式抗原受体嵌合式抗原受体蛋白质工程工程蛋白质工程

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