海军医科大学徐沪济等取得重要工作进展，他们利用同种异体CD19靶向的CAR-T治疗了严重肌炎和系统性硬化症患者，并获得良好的治疗效果。相关研究成果2024年7月15日在线发表于《细胞》杂志上。
据介绍，同种异体嵌合抗原受体（CAR-T）细胞在扩大CAR-T治疗的可及性方面具有巨大的前景，然而同种异体排斥反应的风险阻碍了其应用。
研究人员使用CRISPR-Cas9对健康供体来源的靶向CD19的CAR-T细胞进行基因工程改造，以解决免疫排斥问题，并用这些细胞治疗了一名难治性免疫介导的坏死性肌病患者和两名弥漫性皮肤系统性硬化症患者。该研究已在ClinicalTrials.gov（NCT0585997）上注册。注入的细胞持续了3个多月，在治疗2周内实现了B细胞的完全耗竭。
在6个月的随访期间，研究人员观察到所有三名患者均出现深度缓解，没有细胞因子释放综合征或其他严重不良事件，主要表现为两种疾病的临床反应指数评分分别显著改善，并观察到炎症和纤维化的逆转。
总之，这一研究结果表明，改造后的CAR-T细胞在治疗严重难治性自身免疫性疾病方面具有很高的安全性和有前景的免疫调节作用。
附：英文原文
Title: Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis
Author: Xiaobing Wang, Xin Wu, Binghe Tan, Liang Zhu, Yi Zhang, Li Lin, Yi Xiao, An Sun, Xinyi Wan, Shiyuan Liu, Yanfang Liu, Na Ta, Hang Zhang, Jialin Song, Ting Li, Ling Zhou, Jian Yin, Lingying Ye, Hongjuan Lu, Jinwei Hong, Hui Cheng, Ping Wang, Weiqing Li, Jianfeng Chen, Jin Zhang, Jing Luo, Miaozhen Huang, Lehang Guo, Xiaoming Pan, Yi Jin, Wenjing Ye, Lie Dai, Jian Zhu, Lingyun Sun, Biao Zheng, Dali Li, Yanran He, Mingyao Liu, Huaxiang Wu, Bing Du, Huji Xu
Issue&Volume: 2024-07-15
Abstract: Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expandingthe accessibility of CAR-T therapy, whereas the risks of allograft rejection havehampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targetingCAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treatedone patient with refractory immune-mediated necrotizing myopathy and two patientswith diffuse cutaneous systemic sclerosis with these cells. This study was registeredat ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving completeB cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observeddeep remission without cytokine release syndrome or other serious adverse events inall three patients, primarily shown by the significant improvement in the clinicalresponse index scores for the two diseases, respectively, and supported by the observationsof reversal of inflammation and fibrosis. Our results demonstrate the high safetyand promising immune modulatory effect of the off-the-shelf CAR-T cells in treatingsevere refractory autoimmune diseases.
DOI: 10.1016/j.cell.2024.06.027
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00701-3