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合作CAR的目标是选择性地消除AML并最大限度地减少逃跑

Sascha Haubner¹, Jorge Mansilla-Soto¹, Sarah Nataraj¹

¹Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

|October 6, 2023

概括

这项研究介绍了一种针对急性髓性白血病 (AML) 的新型仿制抗原受体 (CAR) 疗法,该疗法通过共同向ADGRE2和CLEC12A. 这种方法有效地消除了AML细胞,同时最大限度地减少了对正常造血干细胞的毒性.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
分子生物学分子生物学

背景情况:

由于细胞的可变性和与正常干细胞的相似性,急性髓性白血病 (AML) 对CAR疗法构成了挑战.
向AML需要策略,以区分白血病和健康的造血干细胞/原始细胞 (HSPC).

研究的目的:

制定一个CAR战略,以有效地针对AML,降低HSPC毒性.
识别和共同向特定抗原 (ADGRE2和CLEC12A),从而创造一个治疗窗口.

主要方法:

在患者的AML和正常的HSPC中量化ADGRE2和CLEC12A表达.
开发了一种减弱的ADGRE2-CAR与一个CLEC12A-chimeric共刺激受体 (ADCLEC.syn1) 相结合.
在AML异种移植和人性化小鼠模型中测试了ADCLEC.syn1.

主要成果:

ADCLEC.syn1首选针对的是ADGRE2+CLEC12A+AML干细胞,而不是ADGRE2低CLEC12A-HSPCs.
该策略防止了AML模型中的抗原逃逸,并在人性化小鼠中根除了AML.
目标外的HSPC毒性与CD19-CARs可比,并且可以通过干扰素-玛降低来控制.

结论:

目标密度适应的合作CAR准有选择性地消除了AML.
这种方法显示出有可能避免在AML治疗后需要造血救援.

关键词:

在CAR T细胞疗法中.美国国际航空公司 (ICAHT)如果-BETTER 门口.急性骨髓性白血病 (AML) 是一种急性骨髓性白血病.仿制性抗原受体的复制性受体.结合性的目标定位.合作的CAR CAR是一个合作组织.血液中毒性血液中毒性在目标外的毒性.在目标上有毒性

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