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具有增强持久性的CD97导向的CAR-T细胞在多种异种移植模型中消除了急性髓性白血病

Kai Shang¹, Deyu Huang², Jun Liu³

¹Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, China; Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China.

Cell reports. Medicine

|May 27, 2025

概括

这项研究确定CD97是用于急性髓性白血病 (AML) 中的仿真抗原受体 (CAR) -T细胞治疗的有希望的标. 优化的CD97 CAR-T细胞有效地向AML,同时最大限度地减少对健康细胞的损伤.

科学领域:

免疫治疗是一种免疫疗法.
血液瘤学血液瘤学
分子生物学分子生物学

背景情况:

化学抗原受体 (CAR) -T细胞疗法对急性髓性白血病 (AML) 显示出前景.
一个主要的挑战是缺乏AML细胞上的特定抗原标.
由于其在AML细胞上的表达率较高,而不是正常的造血干细胞和原始细胞 (HSPC),因此CD97被提议为潜在的标.

研究的目的:

评估CD97作为在AML中CAR-T细胞治疗的标.
设计CD97特异性的CAR-T细胞,克服兄弟杀戮并增强抗白血病活性.
研究优化CAR-T细胞的疗效背后的机制.

主要方法:

使用CRISPR-Cas9基因编辑,在CAR-T细胞中敲除了CD97 (CD97^KO).
通过突变CD3ζ域,CD97 CAR-T细胞得到了进一步优化.
为了评估疗效和毒性,进行了体外和体内实验 (异种移植模型).
进行了转录分析,以分析CAR-T细胞的行为.

主要成果:

CD97^KO CAR-T细胞有效地消除了AML细胞系和主要AML细胞.
在正常的HSPC中观察到可容忍的毒性.
优化的CD97 CAR-T细胞在体外和体内表现出持续的抗瘤活性.
转录分析表明,在优化的CAR-T细胞中,分化延迟和抗疲劳性.

结论:

CD97是AML中CAR-T细胞治疗的可行和有前途的标.
改造的CD97 CAR-T细胞,特别是优化版本,为AML提供了潜在的治疗策略.
针对CD97的CAR-T细胞治疗的进一步发展需要对AML治疗进行调查.

关键词:

在CD97 CD97 CD97 CD97 CD97 CD97 CD97 急性骨髓性白血病 (AML) 是一种急性骨髓性白血病.仿制性抗原受体的仿制性抗原受体疲疲疲疲疲免疫疗法免疫疗法

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