Dong Ming-Hao, Mei Zhi-Cheng, Zhou Luo-Qi, Heming Michael, Xu Lu-Lu, Liu Yu-Xin, Pang Xiao-Wei, Chu Yun-Hui, Cai Song-Bai, Ye Huan, Shang Ke, Xiao Jun, Meyer Zu Hörste Gerd, Wang Wei, Qin Chuan, Tian Dai-Shi
Department of Neurology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
Med. 2025 Sep 12;6(9):100704. doi: 10.1016/j.medj.2025.100704. Epub 2025 May 26.
Chronic inflammatory demyelinating polyneuropathy (CIDP) presents a significant therapeutic challenge, with up to 15% of patients being refractory to first-line treatments.
Anti-B cell maturation antigen chimeric antigen receptor T (CAR-T) cell therapy was applied to two patients with highly relapsed and refractory CIDP, followed by safety and efficacy evaluation. Multi-omics analyses were performed on samples of peripheral blood mononuclear cells (PBMCs) collected before and after infusion.
Both patients had no severe adverse events and achieved drug-free remission within 6 months post-CAR-T therapy. Patient 1 experienced disease recurrence 12 months post infusion following a severe infection of COVID-19, while patient 2 maintained remission over 24 months. Relapse was accompanied by reactivation of pathogenic B cells and recurrence of autoantibodies/peptides targeting axons or myelin. Metabolic reprogramming of B cells characterized by overglycolysis was linked to disease relapse, which could be modulated by regulatory factor X5.
This study demonstrates the safety and potential of anti-BCMA CAR-T cell therapy in treating refractory CIDP and provides insights into the molecular mechanisms underlying patient responses (ClinicalTrials.gov: NCT04561557).
Ministry of Science and Technology China Brain Initiative grant STI2030-Major Projects 2022ZD0204700 (to W.W.), National Natural Science Foundation of China grants 82371404 and 82071380 (to D.-S.T.) and 82471353 and 82271341 (to C.Q.), Knowledge Innovation Program of Wuhan Shuguang Project 2022020801020454 (to C.Q.), and Key Research and Development Program of Hubei Provincial Department of Science and Technology 2023BCB148 (to D.-S.T.). The clinical trial was funded by Nanjing IASO Biotechnology Co., Ltd.
慢性炎性脱髓鞘性多发性神经病（CIDP）带来了重大的治疗挑战，高达15%的患者对一线治疗无效。
将抗B细胞成熟抗原嵌合抗原受体T（CAR-T）细胞疗法应用于两名高度复发且难治的CIDP患者，随后进行安全性和疗效评估。对输注前后采集的外周血单个核细胞（PBMC）样本进行多组学分析。
两名患者均未出现严重不良事件，且在CAR-T治疗后6个月内实现了无药缓解。患者1在输注后12个月因严重感染新型冠状病毒肺炎而出现疾病复发，而患者2在24个月内维持缓解状态。复发伴随着致病性B细胞的重新激活以及针对轴突或髓鞘的自身抗体/肽的复发。以糖酵解过度为特征的B细胞代谢重编程与疾病复发有关，这可由调节因子X5调节。
本研究证明了抗BCMA CAR-T细胞疗法在治疗难治性CIDP中的安全性和潜力，并提供了对患者反应潜在分子机制的见解（ClinicalTrials.gov：NCT04561557）。
中国科学技术部中国脑计划项目资助STI2030 - 重大项目2022ZD0204700（授予W.W.），国家自然科学基金项目82371404和82071380（授予D.-S.T.）以及82471353和82271341（授予C.Q.），武汉曙光计划知识创新项目2022020801020454（授予C.Q.），湖北省科学技术厅重点研发计划项目2023BCB148（授予D.-S.T.）。该临床试验由南京亿康生物科技有限公司资助。
