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来自带血的iNK T细胞作为全源CAR T细胞治疗的平台

Maison Grefe¹, Abel Trujillo-Ocampo¹, Jelita Clinton¹

¹Department of Hematopoietic Biology & Malignancies, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

Frontiers in immunology

|June 16, 2025

概括

来自带血的不变天然杀手T细胞 (CB-iNK T细胞) 提供了一个有前途的全基性CAR T细胞治疗平台. 这些细胞表现出优异的扩张和抗白血病活性,具有治疗急性髓性白血病的潜在改善安全性.

科学领域:

免疫学免疫学免疫学
细胞疗法细胞疗法
在瘤学瘤学.

背景情况:

不变的自然杀手T (iNK T) 细胞是异种化学抗原受体 (CAR) T细胞治疗的候选者,因为它们缺乏移植对宿主疾病 (GvHD).
成人捐赠者 (AD) iNK T 细胞表现出表型和功能异质性,可能影响CAR T 细胞产品的一致性.
由带血 (CB) 衍生的iNK T细胞提供了捐赠者之间的同质性,统一的CD4+表型,以及记忆人群中的丰富性.

研究的目的:

评估CB衍生的iNK T细胞作为现成的CAR T细胞治疗平台的临床前治疗潜力.
评估CB-iNK T细胞的疗效,这些T细胞是用一个针对急性髓性白血病 (AML) 相关抗原PR1的8F4CAR进行工程的.

主要方法:

用8F4CAR (CB-8F4CAR-iNK T细胞) 进行工程的CB衍生的iNK T细胞的生成和表征.
对CB-8F4CAR-iNK T细胞与AD衍生的对应细胞进行扩张,表型和细胞毒性比较.
对PR1/HLA-A2+AML细胞的细胞毒性的体外评估和对抗白血病活性的体内评估.

主要成果:

与AD-iNK T细胞相比,CB-iNK T细胞显示出更高的扩张能力和更高的CD62L表达.
CB-8F4CAR-iNK T细胞表现出增强的在体内细胞毒性对抗AML点和强大的在体内抗白血病活性.
CB-CAR-iNK T 细胞产生 Th2 偏差的细胞因子,这表明严重的细胞因子释放综合征的风险可能降低.

结论:

源自CB的iNK T细胞由于其一致的表型,优异的扩张和增强的CD62L表达,代表了一个有前途的全源性CAR-T细胞治疗来源.
CB-CAR-iNK T细胞表现出强大的抗白血病疗效,具有潜在的安全性,支持其用于治疗AML.
CB-CAR-iNK T 细胞的免疫调节特性,包括 Th2 偏向细胞因子的产生,有助于它们的治疗潜力和安全性.

关键词:

在CAR T细胞疗法中.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.这是带血,带血.不变的自然杀手T细胞

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