Characterization of stem cell factor gene-modified human natural killer cell line, NK-92 cells: implication in NK cell-based adoptive cellular immunotherapy.
NK-92 cells are effective against a broad range of malignant targets both in vitro and in vivo. Stem cell factor (SCF) is an important early acting cytokine for NK cell development. The characterization and implication in clinic of SCF gene-modified NK-92 cells need to be investigated. SCF cDNA was inserted into pcDNA3 eukaryotic expression vector and the recombinant vector (pcDNA3-SCF) was transfected into NK-92 cells. The SCF gene-modified NK-92 cells (NK92-SCF) were cloned and characterized by cytokine gene expression, proliferation potential, cytotoxic function and surface phenotype. NK92-SCF cells continuously produced a high level of SCF in culture supernatant, which made the cells proliferate significantly more rapidly in response to IL-2 or IL-15 stimulation, the cumulative amount of cells in long-term culture was significantly higher. NK92-SCF cells exerted stronger cytotoxicity against a broad range of target tumor cells than their parent NK-92 cells, which was correlated to the increased expression of cytotoxic effector molecules such as perforin and Fas ligand. NK92-SCF cells became more heterogeneous; the CD56(High) and CD56(Low) subsets appeared, which may, at least partly, explain the increased proliferating and cytotoxic potential of NK92-SCF cells. SCF gene-modified NK-92 cells (NK92-SCF cells) are more promising than their parent cells for adoptive cellular immunotherapy.
Zhang
Jian
J
School of Life Sciences, University of Science and Technology of China, Hefei City, Anhui 230027, PR China.
Sun
Rui
R
Wei
Haiming
H
Zhang
Jianhua
J
Tian
Zhigang
Z
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology; D019089:Stem Cell Factor / Q000235:genetics* / Q000627:therapeutic use*; D014162:Transfection
D007376:Interleukin-2; D015848:Interleukin-5; D019089:Stem Cell Factor