在重症肌肉炎和全身性硬化症患者中向CD19的异性CAR- T治疗
Xiaobing Wang1, Xin Wu1, Binghe Tan2
1Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China; National Key Laboratory for Immunity and Inflammation, Shanghai, China.
Cell
|July 16, 2024
概括
预售的全源CAR-T细胞, 设计以防止排斥, 显示出对自身免疫疾病的希望. 这些工程细胞在患有瘤性肌肉病和全身性硬化症的患者中实现了深度缓解,没有严重的副作用.
科学领域:
- 免疫学
- 细胞治疗
- 遗传学
背景情况:
- 基化学抗原受体 (CAR) -T细胞疗法提供了更广泛的获取潜力,但面临免疫排斥的挑战.
- 使用CRISPR-Cas9的基因工程正在探索克服这些排斥障碍.
研究的目的:
- 在患有重症耐受性自身免疫性疾病的患者中评估基因工程化,全基因的CAR- T细胞的安全性和有效性.
- 评估这些现成的CAR-T细胞的持久性,免疫调节效应和临床结果.
主要方法:
- 使用CRISPR-Cas9基因改造健康的供体T细胞以表达一种针对CD19的CAR.
- 三名患有耐火性自身免疫性疾病的患者 (一个免疫媒介性缩性肌肉病,两个扩散性皮肤全身性硬化症) 接受了工程化CAR- T细胞.
- 在6个月的随访期间,对临床反应,B细胞枯竭,细胞持久性和不良事件进行了监测.
主要成果:
- 输注的CAR- T细胞持续超过3个月,导致B细胞在2周内完全消耗.
- 这三名患者的临床反应得分均显著改善,并实现了深度缓解.
- 在随访期间没有观察到细胞因子释放综合征或其他严重不良事件.
- 发现炎症和纤维化的逆转,支持临床改善.
结论:
- 经过基因工程改造的CAR-T细胞显示出高安全性和有前途的免疫调节效果.
- 这种方法有可能治疗严重的耐药性自身免疫性疾病,扩大CAR-T治疗的可用性.
![Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62334.jpg&w=3840&q=50)
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