针对多发性骨髓瘤的单个VHH导向的BCMA CAR-NK细胞
Quan Ren1, Yingling Zu1, Hongchang Su2
1Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, 450008, China.
Experimental hematology & oncology
|November 28, 2023
概括
针对BCMA的工程自然杀手 (NK) 细胞表现出强大的抗髓瘤活性. 在小鼠模型中,BCMA-CD28-IL15 CAR-NK细胞表现出优越的疗效和延长的存活期,提供了一个有前途的免疫治疗方法.
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:
- 自然杀手 (NK) 细胞被探索为自然杀手 (NK) 细胞.
- 在现货货架上买的.
- 与CAR-T细胞相比,由于较低的细胞因子释放综合征 (CRS) 风险而导致的化学抗原受体 (CAR) 产品.
- BCMA 是多发性骨髓瘤中的向抗原.
研究的目的:
- 为多发性骨髓瘤免疫疗法设计和评估单个VHH导向的抗BCMACAR-NK细胞.
- 为了比较不同CAR结构的疗效,包括不同的细胞内信号域和链区域,具有和没有IL-15协同表达.
主要方法:
- 合成四种具有多种细胞内 (2B4,CD28) 和链 (CD28,IgG1) 域的抗BCMA CAR 结构.
- 宫外IL-15的表达和周围血液NK细胞的lentiviral转导.
- 针对BCMA+瘤细胞的体外细胞毒性测定和使用多发性髓瘤小鼠模型的体内研究.
主要成果:
- 与其他结构相比,BCMA-CD28-IL15 CAR-NK细胞对BCMA+瘤细胞表现出优异的细胞毒性和细胞因子分泌.
- 在MM.1S-Luc小鼠模型中,BCMA-CD28-IL15CAR-NK细胞显著抑制瘤生长和延长存活时间.
- 单个VHH导向的CAR-NK细胞表现出了显著的特定杀伤能力.
结论:
- 工程设计的BCMA特异性CAR-NK细胞,特别是BCMA-CD28-IL15结构,代表了对多发性骨髓瘤的有前途的细胞免疫疗法.
- 这项研究强调了NK细胞作为CAR基疗法的T细胞可行的替代品的潜力.
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