朱瑞民2006-07-262018-07-092006-07-262018-07-092004http://ntur.lib.ntu.edu.tw//handle/246246/28726Lowering the expression of major histocompatibility complex (MHC) molecules is one way tumors evade host immune surveillance. Natural killer (NK) cells are activated by low MHC expression. However, in many tumors, NK cell cytotoxicity is severely suppressed. Immunogene therapy with plasmid IL-6 and plasmid IL-15 (pIL6/pIL15) stimulated NK cells. The plasmids were delivered by muscle electroporation. IL-6 antagonized the inhibitory effect of TGF-β on NK cell cytotoxicity and IL-15 promoted NK cell cytotoxicity. In cell cultures, treatment with IL-6/IL-15 effectively relieved the inhibitory effect of TGF-β and activated NK cell cytotoxicity. IL-6 or IL-15 alone did not enhance or only moderately promoted NK cell cytolytic activity. In BALB/c mice, electroporation with pIL-6/pIL-15 increased the ratio of NK cells in the spleen and promoted NK cell cytotoxicity. pIL-6 or pIL-15 alone did not have a significant effect. In C.B-17 SCID mice, gene therapy with pIL-6/pIL-15 strongly inhibited the establishment, and the growth of established canine transmissible venereal tumor (CTVT), a tumor with low MHC expression and high TGF-β secretion. Treatment with anti-asialo GM-1 antibody depleted NK cells and restored tumorigenicity. We demonstrated that the anti-TGF-β effect of IL-6 was essential, but that stimulation of NK cell cytotoxicity by IL-15 also was necessary to effectively suppress tumor growth. Both IL-6 and IL-15 should be included in a 3 therapeutic regimen against tumors with low MHC expression and high TGF-β secretion.application/pdf184647 bytesapplication/pdfzh-TW國立臺灣大學獸醫學系暨研究所reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/28726/1/922313B002130.pdf