对 NK 细胞进行可扩展的生产工艺开发,以大规模扩张为目标
Takuya Kikuchi1, Ippei Takeuchi1, Hideto Yamaguchi1
1CMC Development, Chemical & Biological Labs, Astellas Pharma, Inc., 5-2-3, Tokodai, Tsukuba-shi, Ibaraki, 300-2698, Japan.
Regenerative therapy
|August 14, 2025
概括
我们开发了一种可扩展的化生物反应器工艺,用于扩大诱导多能干细胞衍生的自然杀手 (NK) 细胞. 这种方法实现了1000倍的扩展,质量始终如一,为现成的NK细胞疗法铺平了道路.
科学领域:
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
- 细胞疗法细胞疗法
背景情况:
- 自然杀手 (NK) 细胞对癌症免疫疗法具有前景,因为它们降低了移植对宿主疾病 (GVHD) 的风险.
- 目前的NK细胞扩张方法使用扩展策略,阻碍了"现成"应用.
- 诱导多能干细胞 (iPSC) 衍生NK细胞的可扩展生物反应器培养仍未得到充分研究.
研究的目的:
- 开发和评估一种可扩展的混合生物反应器工艺,用于iPSC衍生的NK细胞扩张.
- 评估重复刺激和扩张对NK细胞产量和质量的影响.
- 为了证明从实验室扩大NK细胞生产到试点规模的可行性.
主要方法:
- 开发了一种用于iPSC衍生的NK细胞扩张的培养系统.
- 采用用激素抗体和扩张NK细胞刺激的重复循环.
- 评估了使用气化生物反应器的扩大参数,从1L转变为10L.
主要成果:
- 与静态培养相比,杂培养显著增强了NK细胞扩张.
- 通过重复循环保持质量,实现了iPSC衍生的NK细胞的1000倍扩张.
- 成功将生产规模扩大到10升生物反应堆,产生可比的细胞扩张和质量.
结论:
- 展示了一个可扩展的气化动生物反应器工艺,用于iPSC衍生的NK细胞扩张.
- 优化的过程支持稳健的细胞扩张和适合治疗应用的质量.
- 这种可扩展的方法促进了"现成"NK细胞疗法的临床转化.
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