自然杀伤（NK）细胞仅占人体免疫细胞的一小部分，但在免疫系统对抗癌症方面发挥着关键作用。它们能够以自我调节的方式通过几种直接或间接的细胞毒性途径消除异常细胞，这使得它们成为抗癌细胞疗法的有利选择。此外，与其他淋巴细胞不同，同种异体 NK 细胞不会或仅极少引起移植物抗宿主疾病，这为现成疗法打开了大门。然而，迄今为止，NK 细胞的生产面临着一些困难，特别是因为影响关键质量属性 (CQA) 的关键工艺参数 (CPP) 很难识别或关联。有许多不同的培育平台可供选择，它们都有自己的特点、优点和缺点，这进一步增加了定义 CPP 并将其与 CQA 联系起来的难度。我们这篇文章的目标是总结当前有关 NK 细胞扩增 CPP 和 CQA 的知识，因此我们系统地分析了动态和静态培养格式实验的现有文献。我们列出了已确定的 CQA 和 CPP 的列表，并讨论了每个 CPP 在 CQA 监管中的作用。此外，我们可以识别某些 CPP 和 CQA 之间的潜在关系。基于这项系统文献研究的发现可以成为有意义的实验的基础，从而更好地理解过程并最终控制。版权所有 © 2024 国际细胞学会

Natural killer (NK) cells make only a small fraction of immune cells in the human body, however, play a pivotal role in the fight against cancer by the immune system. They are capable of eliminating abnormal cells via several direct or indirect cytotoxicity pathways in a self-regulating manner, which makes them a favorable choice as a cellular therapy against cancer. Additionally, allogeneic NK cells, unlike other lymphocytes, do not or only minimally cause graft-versus-host diseases opening the door for an off-the-shelf therapy. However, to date, the production of NK cells faces several difficulties, especially because the critical process parameters (CPPs) influencing the critical quality attributes (CQAs) are difficult to identify or correlate. There are numerous different cultivation platforms available, all with own characteristics, benefits and disadvantages that add further difficulty to define CPPs and relate them to CQAs. Our goal in this contribution was to summarize the current knowledge about NK cell expansion CPPs and CQAs, therefore we analyzed the available literature of both dynamic and static culture format experiments in a systematic manner. We present a list of the identified CQAs and CPPs and discuss the role of each CPP in the regulation of the CQAs. Furthermore, we could identify potential relationships between certain CPPs and CQAs. The findings based on this systematic literature research can be the foundation for meaningful experiments leading to better process understanding and eventually control.Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.