Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Department of Internal Medicine 3-Rheumatology and Immunology and Deutsches Zentrum Immuntherapie (DZI), Friedrich Alexander Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Lancet Neurol. 2024 Jun;23(6):615-624. doi: 10.1016/S1474-4422(24)00140-6.
Neuroimmunology research and development has been marked by substantial advances, particularly in the treatment of neuroimmunological diseases, such as multiple sclerosis, myasthenia gravis, neuromyelitis optica spectrum disorders, and myelin oligodendrocyte glycoprotein antibody disease. With more than 20 drugs approved for multiple sclerosis alone, treatment has become more personalised. The approval of disease-modifying therapies, particularly those targeting B cells, has highlighted the role of immunotherapeutic interventions in the management of these diseases. Despite these successes, challenges remain, particularly for patients who do not respond to conventional therapies, underscoring the need for innovative approaches.
The approval of monoclonal antibodies, such as ocrelizumab and ofatumumab, which target CD20, and inebilizumab, which targets CD19, for the treatment of various neuroimmunological diseases reflects progress in the understanding and management of B-cell activity. However, the limitations of these therapies in halting disease progression or activity in patients with multiple sclerosis or neuromyelitis optica spectrum disorders have prompted the exploration of cell-based therapies, particularly chimeric antigen receptor (CAR) T cells. Initially successful in the treatment of B cell-derived malignancies, CAR T cells offer a novel therapeutic mechanism by directly targeting and eliminating B cells, potentially overcoming the shortcomings of antibody-mediated B cell depletion. WHERE NEXT?: The use of CAR T cells in autoimmune diseases and B cell-driven neuroimmunological diseases shows promise as a targeted and durable option. CAR T cells act autonomously, penetrating deep tissue and effectively depleting B cells, especially in the CNS. Although the therapeutic potential of CAR T cells is substantial, their application faces hurdles such as complex logistics and management of therapy-associated toxic effects. Ongoing and upcoming clinical trials will be crucial in determining the safety, efficacy, and applicability of CAR T cells. As research progresses, CAR T cell therapy has the potential to transform treatment for patients with neuroimmunological diseases. It could offer extended periods of remission and a new standard in the management of autoimmune and neuroimmunological disorders.
神经免疫学的研究和发展取得了重大进展，特别是在治疗神经免疫性疾病方面，如多发性硬化症、重症肌无力、视神经脊髓炎谱系疾病和髓鞘少突胶质细胞糖蛋白抗体病。仅多发性硬化症就批准了 20 多种药物，治疗变得更加个性化。疾病修饰疗法的批准，特别是针对 B 细胞的疗法，突出了免疫治疗干预在这些疾病管理中的作用。尽管取得了这些成功，但仍存在挑战，特别是对于那些对传统疗法没有反应的患者，这凸显了需要创新方法。
针对 CD20 的奥瑞珠单抗和奥法妥木单抗，以及针对 CD19 的依维珠单抗等单克隆抗体的批准，用于治疗各种神经免疫性疾病，反映了人们对 B 细胞活性的理解和管理方面的进展。然而，这些疗法在阻止多发性硬化症或视神经脊髓炎谱系疾病患者疾病进展或活动方面的局限性，促使人们探索细胞为基础的疗法，特别是嵌合抗原受体（CAR）T 细胞。CAR T 细胞最初在治疗 B 细胞源性恶性肿瘤方面取得了成功，通过直接靶向和消除 B 细胞，提供了一种新的治疗机制，可能克服抗体介导的 B 细胞耗竭的缺点。
下一步是什么？CAR T 细胞在自身免疫性疾病和 B 细胞驱动的神经免疫性疾病中的应用显示出作为一种靶向和持久的选择的潜力。CAR T 细胞自主发挥作用，穿透深部组织并有效地耗尽 B 细胞，特别是在中枢神经系统中。尽管 CAR T 细胞的治疗潜力很大，但它们的应用面临着复杂的后勤和与治疗相关的毒性效应管理等障碍。正在进行和即将进行的临床试验对于确定 CAR T 细胞的安全性、疗效和适用性至关重要。随着研究的进展，CAR T 细胞疗法有可能改变神经免疫性疾病的治疗方法。它可以提供更长的缓解期，并为自身免疫和神经免疫性疾病的治疗提供新标准。
