Method of expanding NK cell and composition for culturing
Provided are a method of ex-vivo culture of natural killer (NK) cells by treating the cells with a reactive oxygen species (ROS) inhibitor and/or a p53 protein inhibitor; and a composition comprising the cultured NK cells. By reducing the activity of ROS and p53 proteins during ex-vivo culture, NK cells may have achieved greater expansion efficiency without altering their anti-tumor cytotoxicity.
1. A method of enhancing NK cell expansion, comprising:
treating natural killer (NK) cells with a p53 inhibitor; or a reactive oxygen species (ROS) inhibitor and a p53 inhibitor, wherein the p53 inhibitor is one or more selected from the group consisting of 2-(2-imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone hydrobromide (pifithrin-α) and pifithrin-μ.
2. The method of claim 1 , wherein NK cells are derived from human peripheral blood mononuclear cells (PBMCs).
3. The method of claim 1 , wherein the ROS inhibitor is one or more selected from the group consisting of 1-(4-hydroxy-3-methoxyphenyl)-ethanone (apocynin), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), pyrrolidine dithiocarbamate (PDTC), glutathione (GSH), catalase, manganese superoxide dismutase (MnSOD), vitamin E, and Quercetin.
4. The method of claim 1 , wherein the inhibitors include trolox and pifithrin-α in a molar ratio of 50 to 150:1.
5. The method of claim 1 , wherein the treatment includes culturing NK cells expanded from PBMCs for 1 to 3 weeks in the presence of the p53 inhibitor; or the ROS inhibitor and the p53 inhibitor.
6. The method of claim 1 , wherein the method comprises: inducing and expanding NK cells from PBMCs; and culturing the expanded NK cells for 1 to 3 weeks in the presence of the p53 inhibitor; or the ROS inhibitor and the p53 inhibitor.