华中科技大学王伟小组宣布他们开发出抗BCMA CAR-T治疗进展性多发性硬化症。这一研究成果发表在2025年10月15日出版的国际学术期刊《细胞》上。

在一项正在进行的1期临床试验（ClinicalTrials.gov: NCT04561557）中，研究小组用抗B细胞成熟抗原（BCMA）嵌合抗原受体T （CAR-T）细胞疗法治疗了5例PMS患者（1例原发性PMS和2例继发性PMS）。仅观察到1级细胞因子释放综合征，所有5例患者均在感染后40天内发生≥3级细胞减少。同时，研究团队检测到CNS室浆细胞耗竭，脑脊液中CAR-T细胞延长扩张和缓解衰竭，以及小胶质细胞活化的衰减。这些发现为抗BCMA CAR-T疗法在推进经前症候群临床管理方面的潜在应用提供了见解。

据了解，进行性多发性硬化症（PMS）的特点是疾病持续进展，缺乏有效的治疗。虽然最近的研究强调了B细胞在PMS发病机制中驱动区隔中枢神经系统（CNS）炎症的重要性，但目前的B细胞消耗疗法，如CD20单克隆抗体，在靶向CNS内的浆细胞方面面临挑战。

附：英文原文

Title: Anti-BCMA CAR-T therapy in patients with progressive multiple sclerosis

Author: Chuan Qin, Ming-Hao Dong, Luo-Qi Zhou, Yun-Hui Chu, Xiao-Wei Pang, Jia-Yi He, Ke Shang, Jun Xiao, Li Zhu, Huan Ye, Song-Bai Cai, Di Wang, Bi-Tao Bu, Gerd Meyer zu Hrste, Chun-Rui Li, Dai-Shi Tian, Wei Wang

Issue&Volume: 2025-10-15

Abstract: Progressive multiple sclerosis (PMS), which is characterized by relentless disease progression, lacks effective treatment. While recent studies have highlighted the importance of B cells in driving compartmentalized central nervous system (CNS) inflammation in PMS pathogenesis, current B cell depletion therapies, such as CD20 monoclonal antibodies, face challenges in targeting plasma cells within the CNS. Here, we treated five patients with PMS (one primary PMS and four secondary PMS) with anti-B cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy in an ongoing phase 1 clinical trial (ClinicalTrials.gov: NCT04561557). Only grade 1 cytokine release syndrome was observed, and all grade ≥3 cytopenias occurred within 40 days post-infusion in all five patients. Meanwhile, we detected plasma cell depletion in CNS compartments, prolonged expansion and relieved exhaustion of CAR-T cells in the cerebrospinal fluid, and attenuation of microglial activation. These findings provided insights into the potential application of anti-BCMA CAR-T therapy for advancing clinical management of PMS.

DOI: 10.1016/j.cell.2025.09.020

Source: https://www.cell.com/cell/abstract/S0092-8674(25)01088-8