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具有IL-21装甲的B7H3CAR-iNKT细胞具有强大的抗瘤作用

Yilin Liu¹, Yuanyuan Dang¹, Chuhan Zhang¹

¹Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China.

|January 5, 2024

概括

用IL-21武装的工程不变NKT (iNKT) 细胞显示增强的抗瘤活性和存活率. 这种组合疗法,使用化抗原受体 (CAR) -iNKT细胞向B7H3,为癌症治疗提供了一个有前途的策略.

科学领域:

免疫学免疫学免疫学
细胞疗法是一种细胞疗法.
在瘤学瘤学.

背景情况:

不变的自然杀手T (iNKT) 细胞对瘤免疫至关重要,但在临床使用中面临扩张和持久性的挑战.
目前的局限性阻碍了iNKT基于细胞的疗法的有效开发和应用.

研究的目的:

为了增强仿真抗原受体 (CAR) 工程iNKT细胞的扩张,持久性和抗瘤疗效.
研究IL-21在增强CAR-iNKT细胞功能和治疗潜力的作用.

主要方法:

从外围血液单核细胞中有效扩张iNKT细胞,使用修饰的细胞因子组合,包括IL-21.
工程iNKT细胞具有针对B7H3.3的第二代CAR.
在体外评估CAR-iNKT细胞活性,STAT3信号和耗尽标记.
在小鼠癌异种移植模型中的治疗疗效的体内评估.

主要成果:

IL-21显著增加了类似记忆的 (CD62L阳性) iNKT细胞的频率.
用IL-21设计的针对B7H3的CAR-iNKT细胞表现出强大的瘤细胞杀伤活性.
IL-21联合表达增强了STAT3信号传递,在体外减少了耗尽标志物,并在体内延长了CAR-iNKT细胞的增殖和生存时间.
在没有细胞因子相关不良事件的小鼠模型中观察到治疗效率的提高.

结论:

IL-21增强了CAR工程iNKT细胞的扩张,记忆表型和效应器功能.
装备IL-21的B7H3CAR-iNKT细胞代表了癌症治疗的有希望和安全的治疗策略.
这种方法克服了iNKT细胞治疗的关键局限性,为临床应用铺平了道路.

关键词:

癌症癌症癌症癌症细胞生物学细胞生物学免疫学免疫学免疫学

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