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利用通用 CAR-T 细胞平台(UniCAR)靶向 B 细胞白血病上的 CD10

英文原题:Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR).

查看英文原题

Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR).

PubMed 2022/04/28(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

表达嵌合抗原受体(CAR)的T细胞无疑是血液系统恶性肿瘤治疗的突破性疗法。尽管取得成功,临床应用也暴露出多项挑战,包括B细胞急性淋巴细胞白血病(B-ALL)中单一靶抗原(如CD19)治疗后复发,以及某些情况下可能较严重的不良反应。因此,要进一步改进B-ALL CAR-T 治疗,显然需要提升安全性的策略并同时靶向多个抗原。本文采用可切换通用CAR(UniCAR)系统,研究将CD10作为B-ALL治疗靶点,以应对这两方面问题。UniCAR平台由两个要素模块化组成:UniCAR-T 细胞和靶向模块(TM);TM将T细胞与肿瘤细胞上的相应靶点连接起来,像“钥匙”一样控制UniCAR-T 细胞的开关状态。本研究表明,配备抗CD10 TM的UniCAR-T 细胞可高效杀伤B-ALL细胞系及患者来源的B-ALL原始细胞,凸显CD10作为B细胞恶性肿瘤新兴治疗靶点的潜力。

展开英文摘要原文

Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases.

Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system.

The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells.

Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies.

论文信息

作者
Mitwasi N、Arndt C、Loureiro LR、Kegler A、Fasslrinner F、Berndt N、Bergmann R、Hořejší V
单位
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, D-01328 Dresden, Germany.Germany
期刊
International journal of molecular sciences2022 Apr 28
原文标识
PubMed 35563312 · DOI 10.3390/ijms23094920