<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "HIGHGLY EFFICIENT ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS FOR CLINICAL USE IN CANCER IMMUNOTHERAPY"^^ . "Natural killer (NK) cells can detect and kill tumor cells and infusion of NK cells to cancer\r\npatients may be a promising option to treat cancer. In this context, ex vivo expansion is used to\r\nproduce large quantities of activated NK cells, because sufficient numbers of these effector cells\r\nare essential for successful NK cell based adoptive cancer immunotherapy. The development of\r\nefficient NK cell expansion protocols and the transfer of these protocols to clinically applicable\r\nmethods represent a major challenge. To overcome this issue, the aim of my project was to\r\ndevelop a clinically applicable method that yields large numbers of highly functional NK cells.\r\nFirst, a fully automated technical process was developed to activate and expand NK cells with\r\n(interleukin) IL-2 and irradiated clinical-grade feeder cells (EBV-LCL). In comparison to the\r\nmanual procedure, the automated process yielded similar NK cells in terms of cell numbers,\r\nsurface marker profile, gene expression and in vitro effector functions. Upon expansion, NK\r\ncells up-regulated functional surface molecules, such as TRAIL, FasL, NKG2D and DNAM-1,\r\nthey increased the production of interferon (IFN)-g and tumor necrosis factor (TNF)-a and they\r\nbecame more cytotoxic against tumor cell lines. Next, because in the used protocol NK cell\r\nexpansion was restricted to a period of 2-4 weeks, a more efficient protocol for long-term\r\nexpansion was developed. Manual NK cell expansion with EBV-LCL and IL-2 induced a 22–\r\nfold mean NK cell expansion after one week that was significantly increased to 53–fold by\r\naddition of IL-21. Furthermore, repeated stimulation with irradiated EBV-LCL and IL-2 and\r\naddition of IL-21 at the initiation of the culture allowed sustained NK cell proliferation with\r\n1011–fold NK cell expansion after six weeks, which is an unprecedented high expansion rate not\r\nachieved by any other method so far. Most importantly, adoptive transfer of NK cells expanded\r\nwith this optimized protocol led to significant inhibition of tumor growth in a melanoma\r\nxenograft mouse model, proofing the therapeutic efficacy of the ex vivo generated NK cells.\r\nThis anti-tumor efficacy was superior over that from conventionally IL-2 activated NK cells,\r\ndemonstrating that the improved NK cell expansion method enhanced not only the quantity but\r\nalso the therapeutic quality of NK cells.\r\nIn conclusion, the outcome of this project is a fully automated process for ex vivo production of\r\nNK cells and an optimized protocol for NK cell expansion with unparalleled efficacy. The\r\nexpanded NK cells possess potent anti-tumor features and showed therapeutic efficacy in a\r\npreclinical melanoma xenograft model. Thereby, the project serves clinical needs and makes it\r\npossible to generate high cell doses of functional NK cells for the use in cancer immunotherapy."^^ . "2016" . . . . . . . "Markus"^^ . "Granzin"^^ . "Markus Granzin"^^ . . . . . . "HIGHGLY EFFICIENT ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS FOR CLINICAL USE IN CANCER IMMUNOTHERAPY (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "HIGHGLY EFFICIENT ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS FOR CLINICAL USE IN CANCER IMMUNOTHERAPY (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "HIGHGLY EFFICIENT ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS FOR CLINICAL USE IN CANCER IMMUNOTHERAPY (Other)"^^ . . . . . . "preview.jpg"^^ . . . "HIGHGLY EFFICIENT ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS FOR CLINICAL USE IN CANCER IMMUNOTHERAPY (Other)"^^ . . . . . . "medium.jpg"^^ . . . "HIGHGLY EFFICIENT ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS FOR CLINICAL USE IN CANCER IMMUNOTHERAPY (Other)"^^ . . . . . . "small.jpg"^^ . . . "HIGHGLY EFFICIENT ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS FOR CLINICAL USE IN CANCER IMMUNOTHERAPY (PDF)"^^ . . . "Granzin_Dissertation.pdf"^^ . . "HTML Summary of #20595 \n\nHIGHGLY EFFICIENT ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS FOR CLINICAL USE IN CANCER IMMUNOTHERAPY\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .