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
一种用于在体内生成 CAR-T 细胞的靶向慢病毒载体
英文原题：A targeting lentiviral vector for generation of CAR-T cells in vivo.
查看英文原题
A targeting lentiviral vector for generation of CAR-T cells in vivo.
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中文摘要
嵌合抗原受体（CAR）T细胞疗法在治疗癌症和自身免疫性疾病方面已展现出显著的治疗效果。然而，目前的CAR-T 细胞疗法需要体外T细胞工程化，这既耗时又成本高昂，增加了整体治疗的复杂性。在本研究中，我们利用工程化的Sindbis病毒包膜，开发了一种慢病毒载体系统，该系统对人T细胞系和原代T细胞具有高度特异性靶向能力，而不靶向其他免疫细胞亚群。值得注意的是，这种T细胞特异性慢病毒载体在体外感染过程中不需要额外的抗CD3/CD28刺激来激活原代T细胞。此外，该慢病毒载体成功地在体内将靶向CD19的CAR分子递送至人原代T细胞。体内生成的CD19-CAR-T 细胞有效介导了B细胞淋巴瘤的清除。总体而言，我们的研究为体内T细胞工程化方法的发展提供了一种有前景的工具。
展开英文摘要原文
Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable therapeutic efficacy in treating cancer and autoimmune diseases.
However, current CAR-T cell therapy requires ex vivo T cell engineering, which is both time-consuming and cost-prohibitive, adding complexity to the overall treatment. In this study, using an engineered Sindbis virus envelope, we developed a lentiviral vector system with high specificity for targeting human T cell line and primary T cells, but not targeting other immune cell subsets.
Notably, this T cell-specific lentiviral vector does not require additional anti-CD3/CD28 stimulation for primary T cell activation during infection in vitro.
Furthermore, the lentiviral vector successfully delivered a CD19-targeting CAR molecule to human primary T cells in vivo. The in vivo generated CD19-CAR-T cells efficiently mediated B cell lymphoma clearance.
Overall, our study provides a promising tool for the development of in vivo T cell engineering approaches.
论文信息
- 作者
- Tuerxunyiming M、Yin JM、Zhu P、Liu M、Fu Z、Zhao Q
- 第一作者单位
- Zhejiang University School of Medicine, Hangzhou, 310058, China.China
- 通讯作者单位
- Department of Endocrinology, Lianshui People's Hospital of Kangda College Affiliated to Nanjing Medical University, Huai'an, 223400, China. 13912063966@163.com.China
- 期刊
- Scientific reports2026 Mar 17
- 原文标识
- PubMed 41844687 · DOI 10.1038/s41598-025-17342-1
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