Ex vivo expansion of natural killer cells with high cytotoxicity by K562 cells modified to co-express major histocompatibility complex class I chain-related protein A, 4-1BB ligand, and interleukin-15.
A large number of natural killer (NK) cells with high function are expected to generate especially in tumor adoptive immunotherapy. Here K562 cells were genetically modified to co-express major histocompatibility complex class I chain-related protein A (MICA), 4-1BB ligand, and IL-15, called K562-MICA-4-1BBL-IL-15. The modified K562 cells not only promoted activation, proliferation, and survival of NK cells, but also enhanced NK cell cytotoxicity. In long-term culture tests, K562-MICA-4-1BBL-IL-15 cells stimulated NK cell to expand mean 550 folds in 24-day culture and to cover from 14.8% of total peripheral blood monoclonal lymphocytes on day 1 to 86.7% on day 24. Prevalent NK cells after expansion enhanced the ability of killing targets and producing interferon gamma (IFN-γ), and kept high expression of activating receptors. The results indicated that K562-MICA-4-1BBL-IL-15 cells would be developed for expansion of NK cells ex vivo and may have important implications for clinical immunotherapy.
Gong
W
W
Department of Immunology, School of Medicine, The Second Clinical Medical College, Yangzhou University, Yangzhou, PR China. gwj1974@263.net
Xiao
W
W
Hu
M
M
Weng
X
X
Qian
L
L
Pan
X
X
Ji
M
M
D053330:4-1BB Ligand / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018920:Coculture Techniques; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019409:Interleukin-15 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*
D053330:4-1BB Ligand; D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; C099187:MHC class I-related chain A; D007371:Interferon-gamma