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. We 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 NKL 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 NKL cells, hIL-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 Mcl-1 as well as the down-regulation of apoptosis genes Bim and Noxa. Moreover, the anti-tumor activity of hIL-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.


CONCLUSIONS
The hIL-15 genetic modification could improve the proliferation, anti-apoptosis and natural cytotoxicity of NKL cells against hepatocarcinoma cells. These data suggest that hIL-15 gene-modified NKL cells could be useful for clinical cancer immunotherapy in the future.
Jiang
W
W
Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Zhang
J
J
Tian
Z
Z
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D005822:Genetic Vectors; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D014161:Transduction, Genetic
D051017:Apoptosis Regulatory Proteins; D019409:Interleukin-15