Next-generation regulatory T-cell therapy to battle transplant rejection

对抗移植排斥的下一代调节性 T 细胞疗法

• 批准号: 2074477
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2074477
• 关键词: Next; generation; regulatory; cell; therapy

The long-term benefits of organ transplantation are hindered by graft rejection, a detrimental process driven by alloreactive T cells. Regulatory T cells (Tregs) are immunosuppressive T cells with a fundamental role in the maintenance of tolerance. Currently, clinical trials at KHP are assessing the safety of polyclonal Tregs in kidney and liver transplanted recipients. Importantly, we and others demonstrated that genetically-engineered donor-specific Tregs are superior to polyclonal Tregs at reducing graft rejection. Chimeric antigen receptors (CARs) are synthetic fusion molecules that translate the binding of specific antigens into delivery of a tailored signal and confer donor-specificity to Tregs. Currently, there is a lack of in vivo information on their whereabouts, longevity, and precise mechanism of action. Rendering CAR Tregs traceable in vivo is urgently required for the translation of this most promising therapy.

器官移植的长期益处受到移植物排斥的阻碍，这是一种由同种异体反应性T细胞驱动的有害过程。调节性T细胞（Regulatory T cells，Tcells）是一种免疫抑制性T细胞，在维持机体免疫耐受中起重要作用。目前，KHP的临床试验正在评估多克隆Tclase在肾和肝移植受者中的安全性。重要的是，我们和其他人证明了基因工程供体特异性Tclase在减少移植排斥反应方面上级多克隆Tclase。嵌合抗原受体（汽车）是合成的融合分子，其将特异性抗原的结合翻译成定制信号的递送，并赋予TcR供体特异性。目前，缺乏关于它们的下落、寿命和精确的作用机制的体内信息。使CAR T细胞在体内可追踪是翻译这种最有前途的疗法所迫切需要的。