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CD19 CAR-T 细胞和 CLL1 CAR-T 细胞中 RQR8 自杀/标志基因的功能验证

英文原题:Functional Validation of the RQR8 Suicide /Marker Gene in CD19 CAR-T Cells and CLL1CAR-T Cells.

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Functional Validation of the RQR8 Suicide /Marker Gene in CD19 CAR-T Cells and CLL1CAR-T Cells.

PubMed 2023/04/22(内容时间) Ann Hematol Q3 · IF 2.3(JCR 2025)

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中文摘要

CAR-T 在血液恶性肿瘤中产生前所未有临床效果,但过继免疫治疗后常出现急性不良事件。自杀基因是一种遗传编码安全机制,可在毒性不可接受时选择性清除过继输入T细胞。本研究将整合CD34和CD20表位的RQR8自杀基因加入CAR-T,使利妥昔单抗可通过抗体依赖性细胞介导细胞毒作用及补体依赖性细胞毒作用清除表达载体/转基因的T细胞。研究在体内外探讨RQR8 CAR-T 功能。作者认为RQR8作为安全开关有望使CAR-T 更安全、成本更低。

展开英文摘要原文

Chimeric antigen receptor T cell therapy (CAR-T) is a novel treatment that has produced unprecedented clinical effects in patients with hematological malignancies. Acute adverse events often occur following adoptive immunotherapy.

Therefore, a suicide gene is helpful, which is a genetically encoded mechanism that allows selective destruction of adoptively transferred T cells in the face of unacceptable toxicity. RQR8 is a gene that integrates CD34 and CD20 epitopes. In our study, we incorporated the suicide gene RQR8 into CAR-T cells, so it enabled rituximab to eliminate vector/transgene-expressing T cells via antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity. In this work, we explored the functionality of RQR8 CAR-T cells in vitro and in vivo.

We believe that RQR8 as a safety switch will make CAR-T cell therapy safer and less costly.

论文信息

作者
Xiong X、Yu Y、Jin X、Xie D、Sun R、Lu W、Wei Y、Guo R
第一作者单位
The First Central Clinical College of Tianjin Medical University, Tianjin, China.China
通讯作者单位
The First Central Clinical College of Tianjin Medical University, Tianjin, China. mingfengzhao@sina.com.China
期刊
Annals of hematology2023 Jun
原文标识
PubMed 37086278 · DOI 10.1007/s00277-023-05227-0