Development of a new immunogene therapy with suppression of O-glycan expression.

概要

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UDP-GaNAc : polypeptide N-acetylgalactosarninyltransferases(GaNAc trapsferases) catalyze the initial reaction in O-linked (mucin type) oligosaccharide biosynthesis. To attempt to inhibit the synthesis of O-glycan, we transfected antisense cDNA of GalNAc transferase-type 1 (GalN Ac-T1) into a human gastric cancer cell line, JRST. A decreased expression of GalNAc-T1 in the level of both mRNA and protein was observed in the resultant transfectants. They demonstrated a significantly increased sensitivity to NK and LAK cells in vitro compared with parental cells and mock transfectants. Although there was no significant difference in in vitro cell proliferation among parental cells, mock transfectants or antisense transfectants, in vivo growth rate of antisense transfectants using SCID mice was clearly lower than that of parental cells and mock transfectants. From these results, we conclude that antisense suppression of GalNAc-T1 could increase the sensitivity of tumor cells to NK and LAK cells, suggesting that this strategy may be of use as a new immunogene therapy.
日本DDS学会の論文