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通过微环 DNA 快速生成 CD19 CAR-T 细胞实现抗肿瘤活性并预防致死性 CAR-B 白血病

英文原题:Rapid generation of CD19 CAR-T cells by minicircle DNA enables anti-tumor activity and prevents fatal CAR-B leukemia.

查看英文原题

Rapid generation of CD19 CAR-T cells by minicircle DNA enables anti-tumor activity and prevents fatal CAR-B leukemia.

PubMed 2023/06/22(内容时间) Cancer Lett Q1 · IF 11.8(JCR 2025)

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中文摘要

使用病毒载体制造嵌合抗原受体(CAR)T细胞成本高且耗时长。此外,病毒转导过程中,CAR编码基因会随机整合至基因组,可能导致致癌或产生危险的CAR肿瘤细胞。本研究采用无病毒、非转基因的小环DNA(mcDNA)载体,在两天内快速制备CD19 CAR-T 细胞。研究进一步在体外和异种移植模型中证明,mcDNA制备的CD19 CAR-T 细胞抗肿瘤作用与病毒载体制备的细胞同样有效。最后,研究显示该制造流程可避免产生致命的CAR肿瘤细胞。综上,研究提供了一种快速、有效且具有治疗安全性的CD19 CAR-T 细胞制备方法,可用于治疗白血病。

展开英文摘要原文

Manufacturing chimeric antigen receptor (CAR)-T cells using viral vectors is expensive and time-consuming.

In addition, during viral transduction, genes encoding CARs are randomly integrated into the genome, which can cause oncogenesis or produce devastating CAR-tumor cells.

Here, using a virus-free and non-transgenic minicircle DNA (mcDNA) vector, we enabled the rapid generation of CD19 CAR-T cells within two days.

Furthermore, we demonstrated in vitro and in xenograft models that the antitumor effects of CD19 CAR-T cells produced by mcDNA are as effective as those produced by viral vectors.

Finally, we showed that our manufacturing process avoids the production of fatal CAR-tumor cells. Taken together, we have provided a fast, effective, and therapeutically safe method for generating CD19 CAR-T cells for the treatment of leukemia.

论文信息

作者
Ye X、Wu Y、Zhang H、Shi L、Zhou Y、Guo S、Dong J、Cai J
第一作者单位
Department of Surgery, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, China; Department of Oncology & Surgery, Hebei General Hospital, 348 West Heping Road, Shijiazhuang, 050051, China; R&D Center, Yetem Biotech Hebei Corp. Ltd., Zhengding-Area of Hebei Free-Trade Zone, Shijiazhuang, 050899, China. Electronic address: xueshuaiye1992@126.com.China
通讯作者单位
Department of Surgery, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, China; Department of Oncology & Surgery, Hebei General Hospital, 348 West Heping Road, Shijiazhuang, 050051, China; R&D Center, Yetem Biotech Hebei Corp. Ltd., Zhengding-Area of Hebei Free-Trade Zone, Shijiazhuang, 050899, China. Electronic address: jianhuicai2001@163.com.China
文献类型
非美国政府资助研究
期刊
Cancer letters2023 Aug 1
原文标识
PubMed 37354981 · DOI 10.1016/j.canlet.2023.216278