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Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis.
Wang, Xiaobing; Wu, Xin; Tan, Binghe; Zhu, Liang; Zhang, Yi; Lin, Li; Xiao, Yi; Sun, An; Wan, Xinyi; Liu, Shiyuan; Liu, Yanfang; Ta, Na; Zhang, Hang; Song, Jialin; Li, Ting; Zhou, Ling; Yin, Jian; Ye, Lingying; Lu, Hongjuan; Hong, Jinwei; Cheng, Hui; Wang, Ping; Li, Weiqing; Chen, Jianfeng; Zhang, Jin; Luo, Jing; Huang, Miaozhen; Guo, Lehang; Pan, Xiaoming; Jin, Yi; Ye, Wenjing; Dai, Lie; Zhu, Jian; Sun, Lingyun; Zheng, Biao; Li, Dali; He, Yanran; Liu, Mingyao; Wu, Huaxiang; Du, Bing; Xu, Huji.
Affiliation
  • Wang X; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China; National Key Laboratory for Immunity and Inflammation, Shanghai, China.
  • Wu X; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China; National Key Laboratory for Immunity and Inflammation, Shanghai, China.
  • Tan B; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, China; BRL Medicine Inc., Shanghai 201109, China.
  • Zhu L; Department of Rheumatology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
  • Zhang Y; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Lin L; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China; National Key Laboratory for Immunity and Inflammation, Shanghai, China.
  • Xiao Y; Department of Radiology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Sun A; Department of Radiology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Wan X; Department of Radiology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Liu S; Department of Radiology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Liu Y; National Key Laboratory for Immunity and Inflammation, Shanghai, China; Department of Pathology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200082, China.
  • Ta N; Department of Pathology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200082, China.
  • Zhang H; Department of Ultrasound, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Song J; Department of Ultrasound, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Li T; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Zhou L; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Yin J; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Ye L; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Lu H; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Hong J; Department of Rheumatology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.
  • Cheng H; Department of Rheumatology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.
  • Wang P; Department of Rheumatology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.
  • Li W; Department of Pathology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Chen J; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, China.
  • Zhang J; Department of Rheumatology and Clinical Immunology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315040, China.
  • Luo J; School of Medicine, Tsinghua University, Beijing 100084, China.
  • Huang M; School of Medicine, Tsinghua University, Beijing 100084, China.
  • Guo L; Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
  • Pan X; Department of Cardiology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • Jin Y; Department of Dermatology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai Key Laboratory of Medical Mycology, Shanghai 200082, China.
  • Ye W; Department of Rheumatology and Immunology, Shanghai Huashan Hospital, Fudan University, Shanghai 200040, China.
  • Dai L; Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
  • Zhu J; Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
  • Sun L; Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
  • Zheng B; BRL Medicine Inc., Shanghai 201109, China.
  • Li D; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, China; BRL Medicine Inc., Shanghai 201109, China.
  • He Y; Committee on Cancer Biology, The University of Chicago, Chicago, IL 60637, USA.
  • Liu M; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, China; BRL Medicine Inc., Shanghai 201109, China. Electronic address: myliu@bio.ecnu.edu.cn.
  • Wu H; Department of Rheumatology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. Electronic address: wuhx8855@zju.edu.cn.
  • Du B; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, China; BRL Medicine Inc., Shanghai 201109, China. Electronic address: bdu@bio.ecnu.edu.cn.
  • Xu H; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China; National Key Laboratory for Immunity and Inflammation, Shanghai, China; School of Medicine, Tsinghua University, Beijing 100084, China; Peking-Tsinghua Center for Life Sciences,
Cell ; 2024 Jul 09.
Article in En | MEDLINE | ID: mdl-39013470
ABSTRACT
Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cell Year: 2024 Type: Article Affiliation country: China
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cell Year: 2024 Type: Article Affiliation country: China