Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany
Fraunhofer Cluster of Excellence for Immune-Mediated Disease, Leipzig, Germany.
RMD Open. 2023 Nov 23;9(4):e002907. doi: 10.1136/rmdopen-2022-002907.
Autoimmune disorders occur when immune cells go wrong and attack the body's own tissues. Currently, autoimmune disorders are largely treated by broad immunosuppressive agents and blocking antibodies, which can manage the diseases but often are not curative. Thus, there is an urgent need for advanced therapies for patients suffering from severe and refractory autoimmune diseases, and researchers have considered cell therapy as potentially curative approach for several decades. In the wake of its success in cancer therapy, adoptive transfer of engineered T cells modified with chimeric antigen receptors (CAR) for target recognition could now become a therapeutic option for some autoimmune diseases. Here, we review the ongoing developments with CAR T cells in the field of autoimmune disorders. We will cover first clinical results of applying anti-CD19 and anti-B cell maturation antigen CAR T cells for B cell elimination in systemic lupus erythematosus, refractory antisynthetase syndrome and myasthenia gravis, respectively. Furthermore, in preclinical models, researchers have also developed chimeric autoantibody receptor T cells that can eliminate individual B cell clones producing specific autoantibodies, and regulatory CAR T cells that do not eliminate autoreactive immune cells but dampen their wrong activation. Finally, we will address safety and manufacturing aspects for CAR T cells and discuss mRNA technologies and automation concepts for ensuring the future availability of safe and efficient CAR T cell products.
自身免疫性疾病是由于免疫细胞出错并攻击身体自身组织而发生的。目前,自身免疫性疾病主要通过广泛的免疫抑制药物和阻断抗体来治疗,这些药物可以控制疾病,但通常不能治愈。因此,严重和难治性自身免疫性疾病患者迫切需要先进的治疗方法,研究人员几十年来一直将细胞疗法视为潜在的治愈方法。在其成功应用于癌症治疗之后,嵌合抗原受体 (CAR) 修饰的工程化 T 细胞的过继转移用于靶标识别,现在可能成为某些自身免疫性疾病的治疗选择。在这里,我们综述了 CAR T 细胞在自身免疫性疾病领域的最新进展。我们将分别介绍抗 CD19 和抗 B 细胞成熟抗原 CAR T 细胞在系统性红斑狼疮、难治性抗合成酶综合征和重症肌无力中用于 B 细胞消除的临床结果。此外,在临床前模型中,研究人员还开发了嵌合自身抗体受体 T 细胞,这些细胞可以消除产生特定自身抗体的单个 B 细胞克隆,以及调节性 CAR T 细胞,它们不会消除自身反应性免疫细胞,而是抑制其错误激活。最后,我们将讨论 CAR T 细胞的安全性和制造方面,并讨论 mRNA 技术和自动化概念,以确保安全有效的 CAR T 细胞产品的未来可用性。