Cell and Gene Therapy Institute (CGTI), Samsung Medical Center, Seoul 06351, Korea.
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06355, Korea.
Int J Mol Sci. 2022 Aug 20;23(16):9426. doi: 10.3390/ijms23169426.
Adaptive natural killer (NK) cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs) can be expanded in vivo in response to human cytomegalovirus (HCMV) infection. Developing a method to preferentially expand this subset is essential for effective targeting of allogeneic cancer cells. A previous study developed an in vitro method to generate single KIR+ NK cells for enhanced targeting of the primary acute lymphoblastic leukemia cells; however, the expansion rate was quite low. Here, we present an effective expansion method using genetically modified K562-HLA-E feeder cells for long-term proliferation of adaptive NK cells displaying highly differentiated phenotype and comparable cytotoxicity, CD107a, and interferon-γ (IFN-γ) production. More importantly, our expansion method achieved more than a 10,000-fold expansion of adaptive NK cells after 6 weeks of culture, providing a high yield of alloreactive NK cells for cell therapy against cancer.
表达自身特异性抑制性杀伤细胞免疫球蛋白样受体 (KIR) 的适应性自然杀伤 (NK) 细胞可以在体内对人巨细胞病毒 (HCMV) 感染作出反应而扩增。开发一种优先扩增这种亚群的方法对于有效靶向同种异体癌细胞至关重要。先前的一项研究开发了一种体外方法来生成单一的 KIR+NK 细胞，以增强对原发性急性淋巴细胞白血病细胞的靶向作用；然而，扩增率相当低。在这里，我们提出了一种使用基因修饰的 K562-HLA-E 饲养细胞的有效扩增方法，用于长期增殖具有高度分化表型和相当细胞毒性、CD107a 和干扰素-γ (IFN-γ) 产生的适应性 NK 细胞。更重要的是，我们的扩增方法在 6 周的培养后实现了适应性 NK 细胞超过 10,000 倍的扩增，为针对癌症的细胞治疗提供了大量同种反应性 NK 细胞。
