一个使用多功能融合蛋白来产生类似记忆的NK细胞用于细胞治疗的"Prime and Expand"策略
Niraj Shrestha1, Michael J Dee1, Pallavi Chaturvedi1
1HCW Biologics Inc., 2929 N. Commerce Parkway, Miramar, FL, 33025, USA.
Cancer immunology, immunotherapy : CII
|July 3, 2024
概括
一种新的"Prime and Expand"方法使用聚变分子显著扩展类似记忆 (ML) 的自然杀手 (NK) 细胞. 这种方法简化了针对血液恶性瘤的现成采用细胞疗法 (ACT) 的制造.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞疗法细胞疗法
- 生物技术是生物技术.
背景情况:
- 采用类似记忆 (ML) 的自然杀手 (NK) 细胞的采用细胞疗法 (ACT) 对血液性恶性瘤有希望.
- 以前的方法使用单个细胞因子进行NK细胞原始化,缺乏体外扩张能力.
- 一个融合分子 (HCW9201) 简化了原始化步骤,但不允许扩张.
研究的目的:
- 开发一种无源细胞的方法,用于ML NK细胞的活体扩张.
- 为NK细胞扩张创造一种新型的融合分子 (HCW9206).
- 为ACT建立临床级ML NK细胞的简化制造工艺.
主要方法:
- 设计并制造了HCW9206,一种含有IL-7,IL-15和IL-21的融合分子.
- 开发了一个两步的方法.
- 总理和扩展扩展.
- 使用HCW9201进行原始化和HCW9206与抗脚架抗体 (HCW9101)进行扩张的协议.
- 用扩张系统培养人类NK细胞14天.
- 评估了细胞扩张,代谢能力,表观遗传修饰,抗瘤活性和体内持久性.
主要成果:
- 使用ML NK细胞实现了300倍以上的扩张.
- 总理和扩展扩展.
- 方法. 方法. 方法.
- 扩张依赖于HCW9206细胞因子和CD16受体的抗体介导参与.
- 扩展的ML NK细胞表现出增强的代谢功能,稳定的IFNG促进体去甲基化,以及卓越的体外和体外抗瘤疗效.
- 在NSG小鼠模型中,细胞表现出更好的持久性.
结论:
- 这是一个很棒的节目,这是一个很棒的节目.
- 总理和扩展扩展.
- 这种策略使得临床级ML NK细胞能够有效,无料细胞扩张.
- 这种方法简化了制造,支持多剂量和现成的采用细胞疗法应用.
- 开发的融合分子和扩展协议代表了NK细胞基癌症免疫疗法的重大进步.
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