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长达十年的白血病缓解与CD4+CAR T细胞的持续

J Joseph Melenhorst^1,2,3,4,5, Gregory M Chen⁶, Meng Wang^7,8,9

¹Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. mej@pennmedicine.upenn.edu.

|February 3, 2022

概括

慢性淋巴细胞白血病的长期CAR T细胞治疗显示持续缓解超过十年. 出现了意想不到的CD4+CAR T细胞群体,表现出持续抗癌反应的细胞毒性和增殖特性.

科学领域:

免疫学
癌症学
细胞治疗

背景情况:

使用仿真抗原受体 (CAR) T 细胞的采用T 细胞疗法对癌症治疗具有前景.
对于注入的CAR T细胞的长期行为和克隆稳定性了解有限.

研究的目的:

在慢性淋巴细胞白血病 (CLL) 患者中研究CD19转向的CAR T细胞的长期持久性,克隆稳定性和特征.
确定与持续抗白血病反应相关的新型CAR T细胞群.

主要方法:

自2010年以来,对两名用CAR T细胞治疗的CLL患者进行了长度研究.
使用流细胞计和单细胞分析检测和表征注入的CAR T细胞.
对CAR T细胞子集的克隆组成和功能属性 (激活,增殖,细胞毒性) 的分析.

主要成果:

在输液后的十多年里,CAR T细胞仍然可检测,这与两名患者的持续完全缓解有关.
在这两名患者中出现了主导的,高度活化的CD4+CAR T细胞群,其特征是细胞毒性功能和增殖.
观察到克隆稳定性,有限数量的克隆在CAR T细胞中占主导地位.
在初始反应阶段,在1名患者中发现了玛三角 CAR T 细胞的扩张.

结论:

可以实现CAR T细胞的长期持续,从而导致CLL持续缓解.
长期抗白血病反应的关键特征是具有细胞毒性潜力的激活CD4+CAR T细胞的出现.
意想不到的CAR T细胞种群,包括玛三角T细胞,可能有助于治疗的疗效,需要进一步的研究.

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