Development of Genetically Engineered Feeder Cells for Natural Killer Cell Expansion

Abstract

Background/aim: To obtain sufficient numbers of high-quality natural killer (NK) cells, we developed feeder cells using synthetic biology techniques.

Materials and methods: K562 cells were engineered to express membrane bound interleukin-2 (mbIL2) or interleukin-13 (mbIL13).

Results: 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.

Conclusion: Our newly developed feeder cells could provide useful tools for NK cell therapy.

Keywords: Feeder cell; NK cell expansion; anti-tumor therapy; mbIL13; mbIL2.