RNA-seq profile of stimulated Tregs containing co-receptor signaling domain variant chimeric antigen receptors (CARs).. RNA-seq profile of stimulated Tregs containing co-receptor signaling domain variant chimeric antigen receptors (CARs).

Initial CAR therapies were designed and tested in conventional T cells, however several recent reports indicate that CAR Tregs may be effective in solid organ transplant or hematopoietic stem cell transplant. Since Tregs have different activation requirements, we sought to characterize the transcriptional profile of Tregs that were transduced with second-generation CARs containing various co-receptor signaling moieties to determine which bestows Tregs with the most desireable properties. Overall design: Human Tregs/Tconv were transduced with second-generation chimeric antigen receptors (CARs) that contain various co-receptor signaling domains, then stimulated via CAR or T cell receptor.

初代嵌合抗原受体（Chimeric Antigen Receptor，CAR）疗法均以常规T细胞（Conventional T cells，Tconv）为靶点进行设计与实验验证，但近期多项研究表明，CAR修饰的调节性T细胞（Regulatory T cells，Tregs）在实体器官移植或造血干细胞移植中或具备有效治疗潜力。鉴于调节性T细胞具有独特的活化需求，本研究拟对转导了携带多种共受体信号结构域的第二代CAR的Tregs进行转录组特征分析，以明确何种结构域可赋予Tregs最优的生物学特性。
整体实验设计：将人源调节性T细胞与常规T细胞转导携带多种共受体信号结构域的第二代嵌合抗原受体，随后分别通过CAR或T细胞受体（T Cell Receptor，TCR）进行刺激。