Fischbach Felix, Pfeffer Lena Kristina, Heesen Christoph, Friese Manuel A
Klinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland.
Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie, Falkenried 94, 20251, Hamburg, Deutschland.
Z Rheumatol. 2025 Jul 10. doi: 10.1007/s00393-025-01676-2.
Chimeric antigen receptor (CAR) T cell therapies were originally developed for the treatment of hematological malignancies; however, they are gaining increasing importance in the treatment of selected individuals with severe, treatment-refractory courses of neuroimmunological diseases. This article discusses the available treatment experiences to date and the potentially promising biotechnological developments in the context of the underlying neuroimmunological pathophysiology.
The spectrum of immunopathology in neuroimmunological diseases ranges from classical autoantibody-mediated autoimmune diseases, such as myasthenia gravis to immunologically complex conditions like multiple sclerosis. The CAR T cell products currently in use target B cells, leading to complete B cell depletion, including autoreactive B cell clones. The therapeutic response, measured by disease activity and biomarkers, varies depending on the underlying immunopathology. The use of CAR T cells in different disease entities has shown a favorable safety profile concerning acute toxicity.
Currently available and emerging CAR T cell therapy approaches open new therapeutic perspectives for neuroimmunological diseases. Larger studies are needed to assess safety, efficacy and long-term effects and to identify individual disease courses that may be suitable for the application of these forms of treatment.
嵌合抗原受体（CAR）T细胞疗法最初是为治疗血液系统恶性肿瘤而开发的；然而，它们在治疗某些患有严重、治疗难治性神经免疫疾病的个体中越来越重要。本文在潜在的神经免疫病理生理学背景下讨论了迄今为止可用的治疗经验以及潜在的有前景的生物技术发展。
神经免疫疾病中的免疫病理学范围从经典的自身抗体介导的自身免疫性疾病，如重症肌无力，到免疫复杂的疾病，如多发性硬化症。目前使用的CAR T细胞产品靶向B细胞，导致B细胞完全耗竭，包括自身反应性B细胞克隆。通过疾病活动和生物标志物衡量的治疗反应因潜在的免疫病理学而异。在不同疾病实体中使用CAR T细胞已显示出关于急性毒性的良好安全性。
目前可用的和正在出现的CAR T细胞疗法为神经免疫疾病开辟了新的治疗前景。需要进行更大规模的研究来评估安全性、疗效和长期影响，并确定可能适合应用这些治疗形式的个体疾病进程。
