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Updated: Jan 11, 2026

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在急性髓性白血病中,MicroRNA-142改善IL1RAP CAR-T细胞活性

Kaito Harada^1,2, Dandan Zhao¹, Miso Park³

¹Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA.

Journal of hematology & oncology

|November 12, 2025

概括

这项研究开发了针对急性髓性白血病 (AML) 的嵌合式抗原受体 (CAR) T 细胞的介质素-1受体辅助蛋白 (IL1RAP). 同时使用miR-142模仿增强了CAR-T细胞的持久性和有效性,在AML模型中显著改善了存活率.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物技术是生物技术.

背景情况:

介素-1受体辅助蛋白 (IL1RAP) 在急性髓性白血病 (AML) 细胞上表达高,但不是正常干细胞.
这种选择性表达使IL1RAP成为在AML中使用仿真抗原受体 (CAR) T细胞治疗的有吸引力的标.

研究的目的:

开发和评估用于AML治疗的新型IL1RAP向性CAR-T细胞.
在AML模型中研究增强CAR-T细胞持久性和抗白血病活性的策略.

主要方法:

开发了针对IL1RAP的CAR-T细胞,使用具有CD28和CD3ζ域的单链Fab (24scFab).
产生了具有突变IL1RAP结合域的控制CAR-T细胞.
在急性髓性白血病 (AML) 细胞系衍生 (CD) 和患者衍生 (PD) 异种移植中测试了CAR-T细胞.
评估的策略包括CD3ζITAM突变和合成miR-142模仿剂 (M-miR-142) 的同时使用.

主要成果:

在AML异种移植模型中,IL1RAP CAR-T细胞显示出强烈的抗白血病活性.
突变的CAR-T细胞证实了目标特异性.
与IL1RAP CAR-T细胞同时使用M-miR-142可显著增加患者衍生异体移植的中位生存期 (对照组为78天,对照组为51天).
IL1RAP-1XX CAR-T细胞在体外持续性得到改善,但在体内没有治疗效益.

结论:

IL1RAP CAR-T细胞治疗是一种有前途的AML治疗方法.
同时使用M-miR-142可以克服白血病引起的免疫抑制,并增强CAR-T细胞的疗效.
这一战略提供了一种新的方法来改善CAR-T细胞在AML中的持久性和有效性.

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相关概念视频

MicroRNAs

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...

MicroRNAs

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...