B cell-directed CAR T cell therapy has fundamentally changed the treatment of hematological malignancies and its scope of application is rapidly expanding to include other diseases such as solid tumors or autoimmune disorders. Therapy-refractoriness remains an important challenge in various inflammatory and non-inflammatory disorders of the CNS. The reasons for therapy failure are diverse and include limited access of current therapies to the CNS, as well as enormous inter- and intraindividual disease heterogeneity. The tissue-penetrating properties of CAR T cells make them a promising option to overcome this problem and to tackle pathologies directly within the CNS. First application of B cell-directed CAR T cells in neuromyelitis optica spectrum disorder and multiple sclerosis patients has lately revealed promising outcomes, expanding the potential of CAR T cell therapy to encompass CNS diseases. Additionally, the optimization of CAR T cells for the therapy of gliomas is a growing field. As a further perspective, pre-clinical data reveal potential benefits of CAR T cell therapy also in the treatment of primary neurodegenerative diseases such as Alzheimer's disease. Considering the biotechnological optimizations in the field of T cell engineering, such as the extension to target different antigens or the variation of the modified T cell subtype, new and promising fields of application for CAR T cells are rapidly opening up. These innovations offer the potencial to address the complex pathophysiological properties of CNS diseases. To optimally utilize CAR T cell therapy for CNS diseases in the future while minimizing therapy risks, there is a need for further mechanistic research as well as prospective controlled trials to seriously assess the disease and patient-specific risk-benefit ratio.

中文翻译：

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CAR T 细胞疗法在中枢神经系统疾病中的现状和前景


B 细胞导向的 CAR T 细胞疗法从根本上改变了血液系统恶性肿瘤的治疗，其应用范围正在迅速扩大到包括其他疾病，如实体瘤或自身免疫性疾病。治疗难治性仍然是 CNS 各种炎症和非炎症性疾病的重要挑战。治疗失败的原因多种多样，包括当前疗法对 CNS 的可及性有限，以及个体间和个体内疾病的巨大异质性。CAR T 细胞的组织穿透特性使其成为克服这个问题并直接在 CNS 内处理病理的有前途的选择。B 细胞定向 CAR T 细胞在视神经脊髓炎谱系疾病和多发性硬化症患者中的首次应用最近显示出有希望的结果，扩大了 CAR T 细胞疗法涵盖 CNS 疾病的潜力。此外，优化 CAR T 细胞治疗神经胶质瘤是一个不断增长的领域。从更进一步的角度来看，临床前数据揭示了 CAR T 细胞疗法在治疗阿尔茨海默病等原发性神经退行性疾病方面的潜在益处。考虑到 T 细胞工程领域的生物技术优化，例如针对不同抗原的扩展或修饰的 T 细胞亚型的变异，CAR T 细胞新的和有前途的应用领域正在迅速开辟。这些创新为解决 CNS 疾病复杂的病理生理特性提供了潜力。 为了在未来以最佳方式利用 CAR T 细胞疗法治疗 CNS 疾病，同时最大限度地降低治疗风险，需要进一步的机制研究和前瞻性对照试验，以认真评估疾病和患者特异性风险收益比。