CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Neurological implications of chimeric antigen receptor-T cell therapy.
Neurological implications of chimeric antigen receptor-T cell therapy.
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嵌合抗原受体(CAR)-T细胞疗法已经改变了复发/难治性血液系统恶性肿瘤的治疗格局,目前正被改造用于治疗严重的B细胞介导的自身免疫性疾病,包括神经免疫性疾病。其吸引力在于能够在淋巴组织和靶器官内实现深度且持久的B细胞清除,并有可能诱导长期的无治疗缓解。与此同时,更广泛的应用受到严重毒性的限制,尤其是神经系统并发症,如免疫效应细胞相关神经毒性综合征(ICANS),以及近年来被认识到的运动、小脑、颅神经和周围神经综合征。在这篇综述中,我们概述了CAR-T 细胞疗法的生物学原理,并总结了神经免疫学领域的新兴经验。
我们综合肿瘤学和早期自身免疫试验的数据,描述CAR-T 细胞相关神经毒性的临床谱、发生时间和推测机制,并将ICANS与较晚出现且更为局灶性的毒性相区分。随着CAR-T 细胞疗法从癌症中心走向难治性神经免疫性疾病患者的诊疗,神经科医生需要对其治疗前景和神经系统风险都有详细的了解,而多学科团队内的紧密协作对于安全实施这些治疗至关重要。
Chimeric antigen receptor (CAR)-T cell therapies have transformed the management of relapsed or refractory haematological malignancies and are now being adapted for severe B-cell mediated autoimmune disease, including neuroimmunological disorders. Their appeal lies in deep and durable B-cell depletion within lymphoid tissues and target organs, with the potential to induce long-lasting, treatment-free remission.
At the same time, broader application is constrained by serious toxicities, in particular, neurological complications such as immune effector cell-associated neurotoxicity syndrome (ICANS) and more recently recognised movement, cerebellar, cranial nerve and peripheral nerve syndromes. In this review, we outline the biological principles of CAR-T cell therapy and summarise the emerging experience in neuroimmunology.
We draw on data from both oncology and early autoimmune trials to describe the clinical spectrum, timing and proposed mechanisms of CAR-T cell-related neurotoxicity and to distinguish ICANS from later and more focal toxicities.
As CAR-T cell therapies move from cancer centres into the care of patients with refractory neuroimmunological disease, neurologists will need a detailed understanding of both their therapeutic promise and their neurological risks, and close collaboration within multidisciplinary teams will be essential to deliver these treatments safely.
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