Characterization of interleukin-15 gene-modified human natural killer cells: implications for adoptive cellular immunotherapy.
OBJECTIVE
Natural killer (NK)-92 cells are effective against a broad range of malignant targets both in vitro and in vivo. Interleukin-15 (IL-15) is an important cytokine for NK cell development and differentiation. IL-15 gene-modified NK-92 cells need to be characterized and their clinical implications investigated.


METHODS
IL-15 cDNA was inserted into a pcDNA3 eukaryotic expression vector and the recombinant vector (pcDNA3-IL15) was tranfected into NK-92 cells. The IL-15 gene-modified NK-92 cells (NK92-IL15) were cloned and characterized with regard to their cytokine production, proliferation, cytotoxicity and surface phenotype.


RESULTS
NK92-IL15 cells continuously produced a high level of IL-15 in culture supernatant, which made the cells proliferate significantly more rapidly in response to stimulation with low doses of IL-2 or IL-15; the cumulative number of cells in long-term culture was also significantly higher. NK92-IL15 cells became adherent to plastic and their expression of CD54 increased, which may explain their improved proliferating potential, like adherent NK cells. NK92-IL15 cells were more strongly cytotox against a broad range of target tumor cells than the parent NK-92 cells, and this increased cytotoxicity was correlated to the increased expression of cytotoxic effector molecules, such as perforin, Fas ligand and IFNgamma, and up- or down-regulated expression of activating or inhibitory NK cell receptors (NKG2D or NKG2A/CD94).


CONCLUSIONS
These results demonstrate that NK92-IL15 cells are promising for adoptive cellular immunotherapy.
Zhang
Jian
J
School of Life Sciences, University of Science and Technology of China, Hefei City, Anhui, China.
Sun
Rui
R
Wei
Haiming
H
Zhang
Jianhua
J
Tian
Zhigang
Z
D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D019409:Interleukin-15 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology*
D019409:Interleukin-15