上海科技大学知识管理系统

The present invention provides a chimeric antigen receptor, comprising, connected in sequence : an extracellular structural domain, a transmembrane structural domain, and an intracellular structural domain. The extracellular structural domain comprises an antigen recognition region; the intracellular structural domain comprises a costimulatory signal transduction region and a CD3ζ intracellular region connected in sequence to form a costimulatory signal transduction region-CD3ζ intracellular region; the costimulatory signal transduction region-CD3ζ intracellular region is a polypeptide formed by mutation of lysine in a wild-type costimulatory signal transduction region-CD3ζ intracellular region into arginine. The present invention provides a method for the optimization and transformation of CAR-T. All lysine sites in the intracellular segment of CAR are mutated into arginine, thereby blocking the ubiquitination modification produced by CAR after antigenic stimulation. The policy is applicable to different CARs and transforming different intracellular costimulatory domains, and particularly, provides a solving idea for the problem of poor proliferation of CAR-T in solid tumors.

本发明提供了一种嵌合抗原受体，其包括依次连接的细胞外结构域，跨膜结构域和细胞内结构域。 胞外结构域包括抗原识别区； 胞内结构域包括依次连接的共刺激信号转导区和CD3胞内区，形成共刺激信号转导区-CD3胞内区； 共刺激信号转导区-CD3胞内区是由野生型共刺激信号转导区-CD3胞内区中的赖氨酸突变为精氨酸形成的多肽。 本发明提供了一种优化改造CAR-T的方法。 CAR胞内片段中的所有赖氨酸位点突变为精氨酸，从而阻断CAR在抗原刺激后产生的泛素化修饰。 该策略适用于不同的CAR和转化不同的细胞内共刺激结构域，特别是为实体瘤中CAR-T增殖不良的问题提供了一种解决思路。