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
利用病毒模拟融合性纳米囊泡体内生成 CAR-T 细胞
英文原题：In vivo production of CAR-T cells using virus-mimetic fusogenic nanovesicles.
查看英文原题
In vivo production of CAR-T cells using virus-mimetic fusogenic nanovesicles.
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中文摘要
表达嵌合抗原受体（CAR）的工程化T细胞在B细胞恶性肿瘤治疗中具有较高缓解率，对多种疾病也有治疗潜力。然而，复杂的CAR-T 细胞体外生产流程限制了其应用。本文利用病毒模拟融合纳米囊泡（FuNV），通过膜融合介导的CAR蛋白递送，在体内制备CAR-T 细胞。简言之，FuNV表面展示抗CD3单链可变片段，并采用源自麻疹病毒或呼肠孤病毒融合蛋白的T细胞融合蛋白进行改造。FuNV可在体内与T细胞膜高效融合，进而将装载的抗CD19（αCD19）CAR蛋白递送至T细胞上，制备CD19 CAR-T 细胞。无论单独使用还是联合抗OX40抗体，这些CD19 CAR-T 细胞均可治疗B细胞淋巴瘤，且不诱发细胞因子释放综合征。因此，该策略提供了一种在体内将T细胞工程化为CAR-T 细胞的新方法，也可进一步用于递送其他治疗性膜蛋白。
展开英文摘要原文
Engineered T cells expressing chimeric antigen receptor (CAR) exhibit high response rates in B-cell malignancy treatments and possess therapeutic potentials against various diseases.
However, the complicated ex vivo production process of CAR-T cells limits their application.
Herein, we use virus-mimetic fusogenic nanovesicles (FuNVs) to produce CAR-T cells in vivo via membrane fusion-mediated CAR protein delivery. Briefly, the FuNVs are modified using T-cell fusogen, adapted from measles virus or reovirus fusogens via displaying anti-CD3 single-chain variable fragment.
The FuNVs can efficiently fuse with the T-cell membrane in vivo, thereby delivering the loaded anti-CD19 ( CD19) CAR protein onto T-cells to produce CD19 CAR-T cells. These CD19 CAR-T cells alone or in combination with anti-OX40 antibodies can treat B-cell lymphoma without inducing cytokine release syndrome.
Thus, our strategy provides a novel method for engineering T cells into CAR-T cells in vivo and can further be employed to deliver other therapeutic membrane proteins.
论文信息
- 作者
- Zhao G、Zhang Y、Xu CF、Wang J
- 第一作者单位
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China.China
- 通讯作者单位
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, China. Electronic address: mcjwang@scut.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Science bulletin2024 Feb 15
- 原文标识
- PubMed 38072706 · DOI 10.1016/j.scib.2023.11.055