Functional characterization of interleukin-15 gene transduction into the human natural killer cell line NKL

Background Genetic modification of natural killer (NK) cells is a potential approach to gene-based immunotherapy of cancer. I've created human interleukin-15 (hIL-15) gene-modified NKL cells and investigated their functional characterization in vitro. Methods A recombinant vector (pcDNA3-IL15) or control vector (pcDNA3) was transferred into AWL cells by an electroporation method. Standard reverse transcriptase-polymerase chain reaction (RT-PCR), flow cytometry and MTT methods were performed for NK cell proliferation, apoptosis, cytotoxicity assays and gene expression tests. Results Compared with parental AWL cells, bIL-15 gene modification promoted NK cell proliferation at low doses of IL-2 and inhibited cell apoptosis, which was associated with the up-regulation of anti-apoptosis genes Bcl-2, Bcl-xl and Mel-7 as well as the down-regulation of apoptosis genes Bim and Noxa. Moreover, the anti-tumor activity of bIL-15 gene-transduced NKL cells against human hepatoma cancer cell line HepG2, H7402 and PLC/PRF-5 cells was enhanced, at least partly, through increasing expression of cytotoxicity-associated genes, including interferon (IFN)-gamma, perforin and FasL. Discussion The hIL-15 genetic modification could improve the proliferation, antiapoptosis and natural cytotoxicity of AWL cells against hepatocarcinoma cells. These data suggest that hIL- 15 gene-modified AWL cells could be useful for clinical cancer immunotherapy in the future.