The expansion of polyclonal T regulatory cells (Tregs) offers great promise for the treatment of immune-mediated diseases, such as multiple sclerosis (MS). However, polyclonal Tregs can be non-specifically immunosuppressive. Based on the advancements with chimeric antigen receptor (CAR) therapy in leukemia, we previously engineered Tregs to express a T-cell receptor (TCR) specific for a myelin basic protein (MBP) peptide. These TCR-engineered specific Tregs suppressed the proliferation of MBP-reactive T effector cells and ameliorated myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). Herein, we extend this approach by creating human regulatory T cells expressing functional single-chain chimeric antigen receptors (scFv CAR), targeting either MBP or MOG. These scFv CAR-transduced Tregs retained FoxP3 and Helios, characteristic of Treg cells, after long-term expansion in vitro. Importantly, these engineered CNS targeting CAR-Tregs were able to suppress autoimmune pathology in EAE, demonstrating that these Tregs have the potential to be used as a cellular therapy for MS patients.

多克隆调节性 T 细胞 (Tregs) 的扩增为治疗多发性硬化症 (MS) 等免疫介导疾病提供了广阔前景。然而，多克隆 Treg 可能是非特异性免疫抑制的。基于白血病嵌合抗原受体 (CAR) 疗法的进展，我们之前设计了 Tregs 以表达对髓鞘碱性蛋白 (MBP) 肽特异的 T 细胞受体 (TCR)。这些 TCR 工程特异性 Treg 抑制 MBP 反应性 T 效应细胞的增殖并改善髓鞘少突胶质细胞糖蛋白 (MOG) 诱导的实验性自身免疫性脑脊髓炎 (EAE)。在这里，我们通过创建表达功能性单链嵌合抗原受体 (scFv CAR) 的人类调节性 T 细胞来扩展这种方法，靶向 MBP 或 MOG。体外。重要的是，这些针对 CAR-Tr​​eg 的工程化 CNS 能够抑制 EAE 中的自身免疫病理学，证明这些 Treg 有可能用作 MS 患者的细胞疗法。