CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CAR-T 细胞中 GM-CSF 的 RNA 沉默减少多种炎症细胞因子的分泌
英文原题：RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines.
查看英文原题
RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines.
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中文摘要
CAR-T 已成为血液肿瘤研究热点，但可能引起细胞因子释放综合征和神经毒性等免疫治疗相关不良反应。既往研究发现敲除CAR-T 中的GM-CSF可预防不良反应，但需要额外转染步骤。本研究将GM-CSF shRNA表达盒直接插入CAR载体，以抑制CAR-T 细胞中的GM-CSF表达。降低GM-CSF可减少多种促炎细胞因子水平，同时不损害杀伤能力。该方法无需复杂的额外转染，使GM-CSF敲低CAR-T 制备更便于临床应用。
展开英文摘要原文
Chimeric antigen receptor T (CAR-T) cell therapy has become a research hotspot in the field of hematological malignancies.
However, CAR-T cell therapy can lead to immunotherapy-associated side effects including cytokine release syndrome and neurotoxicity. Gene depletion of GM-CSF in CAR-T cells was found preventive against adverse effects, but additional transfections were required to produce CAR-T cells. In this study, we interrupted GM-CSF expression in CAR-T cells by inserting the GM-CSF shRNA-expression cassette in the CAR vector.
Reduction of GM-CSF in CAR-T cells could decrease the level of several proinflammatory cytokines without hampering the killing capacity. The manufacture of GM-CSF knockdown CAR-T cells does not require complicated transfections, which makes it more practical and feasible for clinical application.
论文信息
- 作者
- Shang S、Chen Y、Yang X、Yang Y、Wang W、Wang Y
- 第一作者单位
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Rui Jin Hospital, National Research Center for Translational Medicine at Shanghai, Shanghai Jiao Tong University School of Medicine, 200000, Shanghai, China.China
- 通讯作者单位
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Rui Jin Hospital, National Research Center for Translational Medicine at Shanghai, Shanghai Jiao Tong University School of Medicine, 200000, Shanghai, China. yywang@shsmu.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Investigational new drugs2023 Apr
- 原文标识
- PubMed 36988829 · DOI 10.1007/s10637-023-01344-9
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