上海科技大学知识管理系统

The present invention provides a chimeric antigen receptor, which includes : an extracellular domain, a transmembrane domain, and an intracellular domain connected in sequence. The extracellular domain includes an antigen recognition region; the intracellular domain includes a costimulatory signaling region and a CD3ζ intracellular region that are connected in sequence, to form a costimulatory signaling region-CD3ζ intracellular region; and the costimulatory signaling region-CD3ζ intracellular region is a polypeptide formed by mutation of lysine in a wild-type costimulatory signaling region-CD3ζ intracellular region into arginine. The present invention provides a method for optimization and modification of CAR-T, in which all lysine sites in an intracellular segment of CAR are mutated into arginine, thereby blocking ubiquitination modification of the CAR after antigen challenge. This strategy is applicable to different CARs and changing different intracellular costimulatory domains, and in particular provides a solution to 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：依次连接的胞外结构域，跨膜结构域和胞内结构域。 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区和CD3胞内区，以形成共刺激信号区-CD3胞内区； 共刺激信号区-CD3胞内区是由野生型共刺激信号区-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和修饰CAR-T的方法，其中CAR细胞内片段中的所有赖氨酸位点突变为精氨酸，从而在抗原攻击后阻断CAR的泛素化修饰。 该策略适用于不同的CAR和改变不同的细胞内共刺激结构域，特别是解决了实体瘤中CAR-T增殖不良的问题。