Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Anticancer Res. 2023 Sep;43(9):3897-3904. doi: 10.21873/anticanres.16577.
BACKGROUND/AIM: To obtain sufficient numbers of high-quality natural killer (NK) cells, we developed feeder cells using synthetic biology techniques.
K562 cells were engineered to express membrane bound interleukin-2 (mbIL2) or interleukin-13 (mbIL13).
The incubation of human primary NK cells isolated from peripheral blood mononuclear cells (PBMCs) with these feeder cells significantly increased the number of activated NK cells compared to K562 parental cells. Fluorescence-activated cell sorting (FACS) analysis demonstrated that NKG2D activating receptors were abundant on the surface of NK cells expanded by K562-mbIL2 or mbIL13 cells. NK cells expanded on K562-mbIL2 or mbIL13 lysed cancer cells more effectively than those cultured with normal K562 cells. Using NK cells incubated with our feeder cells, we developed anti-CD19 chimeric antigen receptor (CAR)-NK cells. They showed robust cytotoxic effect against CD19 positive cancer cell line.
Our newly developed feeder cells could provide useful tools for NK cell therapy.
背景/目的：为了获得足够数量的高质量自然杀伤 (NK) 细胞，我们使用合成生物学技术开发了饲养细胞。
将 K562 细胞工程改造为表达膜结合白细胞介素 2 (mbIL2) 或白细胞介素 13 (mbIL13)。
与 K562 亲本细胞相比，将这些饲养细胞与从外周血单核细胞 (PBMC) 中分离的人原代 NK 细胞孵育可显著增加活化 NK 细胞的数量。荧光激活细胞分选 (FACS) 分析表明，NK 细胞表面表达丰富的 NKG2D 激活受体，这些 NK 细胞是由 K562-mbIL2 或 mbIL13 细胞扩增的。与在正常 K562 细胞中培养的 NK 细胞相比，在 K562-mbIL2 或 mbIL13 细胞上扩增的 NK 细胞能更有效地裂解癌细胞。使用与我们的饲养细胞孵育的 NK 细胞，我们开发了抗 CD19 嵌合抗原受体 (CAR)-NK 细胞。它们对 CD19 阳性癌细胞系表现出强大的细胞毒性作用。
我们新开发的饲养细胞可为 NK 细胞治疗提供有用的工具。
