干白素-21工程通过丰富的代谢途径增强了针对B细胞淋巴瘤的CD19特异性CAR-NK细胞活性
Bailin He1,2, Hong Chen1,2, Jiaxu Wu3
1Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Experimental hematology & oncology
|April 2, 2025
概括
介质素-21 (IL-21) 增强了B细胞恶性瘤的化学抗原受体 (CAR) -NK细胞疗法. 与IL-15相比,具有IL-21的CAR-NK细胞表现出更好的持久性和优越的抗瘤活性.
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:
- 化学抗原受体 (CAR) -NK细胞疗法在B细胞恶性瘤中显示出前景.
- 目前,干白素-15 (IL-15) 正在CAR-NK细胞治疗中使用.
- 干白素-21 (IL-21) 在CAR-NK细胞治疗中的作用尚未被探索.
研究的目的:
- 为了研究IL-21对CAR-NK细胞治疗的影响.
- 为了比较用IL-21与IL-15进行工程的CAR-NK细胞的疗效.
主要方法:
- 构建的CD19特异性CAR具有4-1BB共刺激域和IL-21或IL-15.
- 转化了来自外围血液的NK细胞,以产生CAR-21和CAR-15NK细胞.
- 评估了表型特征,转录组特征,功能和抗瘤活性.
主要成果:
- 在CAR-21NK细胞中,IFN-γ,TNF-α和Granzyme B的产生和脱粒度增加.
- CAR-21 NK细胞表现出增强的细胞毒性活性和改善体内持久性.
- 在异种移植模型中,IL-21联合表达抑制了瘤生长,延长了存活时间.
结论:
- 具有IL-21的CD19特异性CAR-NK细胞与具有IL-15的细胞相比,显示出更高的持久性和抗瘤活性.
- 经IL-21工程的CAR-NK细胞代表了对B细胞恶性瘤的有前途的治疗策略.
- 在CAR-21NK细胞中,明显的转录基因特征突出显示了增强的细胞因子,细胞毒性和代谢信号传递.
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