Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL

Zhang, Jiqin; Hu, Yongxian; Yang, Jiaxuan; Li, Wei; Zhang, Mingming; Wang, Qingcan; Zhang, Linjie; Wei, Guoqing; Tian, Yue; Zhao, Kui; Chen, Ang; Tan, Binghe; Cui, Jiazhen; Li, Deqi; Li, Yi; Qi, Yalei; Wang, Dongrui; Wu, Yuxuan; Li, Dali; Du, Bing; Liu, Mingyao; Huang, He

doi:10.1038/s41586-022-05140-y

articleNatureAug 31, 2022HYBRID OA

Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL

JZJiqin Zhang YHYongxian Hu JYJiaxuan Yang WLWei Li MZMingming Zhang

East China Normal University · Zhejiang Chinese Medical University · +4 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Abstract Recently, chimeric antigen receptor (CAR)-T cell therapy has shown great promise in treating haematological malignancies 1–7 . However, CAR-T cell therapy currently has several limitations 8–12 . Here we successfully developed a two-in-one approach to generate non-viral, gene-specific targeted CAR-T cells through CRISPR–Cas9. Using the optimized protocol, we demonstrated feasibility in a preclinical study by inserting an anti-CD19 CAR cassette into the AAVS1 safe-harbour locus. Furthermore, an innovative type of anti-CD19 CAR-T cell with PD1 integration was developed and showed superior ability to eradicate tumour cells in xenograft models. In adoptive therapy for relapsed/refractory aggressive B cell…

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346

total citations

FWCI: 32.03
Percentile: 100%
References: 54

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Authors

22

Topics & keywords

Topics

Keywords

Chimeric antigen receptor
Electroporation
CD19
Lymphoma
Genetic enhancement
T cell
Cell therapy
Medicine

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