Abstract：
Graves\' disease (GD) is a prominent antibody-mediated autoimmune disorder characterized by stimulating antibodies (TRAb) that target the thyroid-stimulating hormone receptor (TSHR). Targeting and eliminating TRAb-producing B lymphocytes hold substantial therapeutic potential for GD. In this study, we engineered a novel chimeric antigen receptor T cell (CAR-T) therapy termed TSHR-CAR-T. This CAR-T construct incorporates the extracellular domain of the TSH receptor fused with the CD8 transmembrane and intracellular signal domain (4-1BB). TSHR-CAR-T cells demonstrated the ability to recognize and effectively eliminate TRAb-producing B lymphocytes both in vitro and in vivo. Leveraging this autoantigen-based chimeric receptor, our findings suggest that TSHR-CAR-T cells offer a promising and innovative immunotherapeutic approach for the treatment of antibody-mediated autoimmune diseases, including GD.
摘要：
Graves病(GD)是一种突出的抗体介导的自身免疫性疾病,其特征是靶向促甲状腺激素受体(TSHR)的刺激抗体(TRAb)。靶向和消除产生TRAb的B淋巴细胞对GD具有重要的治疗潜力。在这项研究中,我们设计了一种称为TSHR-CAR-T的新型嵌合抗原受体T细胞（CAR-T）疗法。该CAR-T构建体包含与CD8跨膜和细胞内信号结构域融合的TSH受体的细胞外结构域(4-1BB)。TSHR-CAR-T细胞表现出在体外和体内识别并有效消除产生TRAb的B淋巴细胞的能力。利用这种基于自身抗原的嵌合受体，我们的研究结果表明，TSHR-CAR-T细胞为治疗抗体介导的自身免疫性疾病提供了一种有前途的创新的免疫治疗方法，包括GD。
