Resistance of pancreatic carcinoma cells is reversed by coculturing NK-like T cells with dendritic cells pulsed with tumor-derived RNA and CA 19-9

Immunization with defined tumor antigens is limited to the small number of cancers in which specific tumor antigens have been defined but insufficient tumor material is available to produce an antitumor vaccine. In this study , we investigated whether pulsing dendritic cells (DC) using a liposomal tr ansfer technique with a pancreatic tumor cell line-derived RNA can effectiv ely activate NK-like T cells and tumor immunity. Pulsed DC were cocultured with NK-like T cells, i.e., CD3(+)CD56(+) cells, as immunologic: effector c ells. Target cells resistant to NK-like T-cell-mediated lysis were used. To tal tumor-derived RNA transfected into DC was found to completely reverse t umor cell resistance. Total tumor RNA transfection (30 mug) was found to be superior to poly(A)(+) RNA transfection (5 mug) in inducing NK-like T lymp hocytes. Interestingly, additional pulsing of DC with the CA 19-9 peptide i n a CA 19-9-positive cell line further increased the sensitivity of pancrea s carcinoma cells to NK-like T cells. Treatment of tumor RNA with RNase com pletely blocked the effect of RNA-transfected DC on NK-like T cells, sugges ting that intact tumor-derived RNA is needed for reversal of tumor cell res istance. In conclusion, coculture of NK-like T cells with DC transfected wi th pancreatic tumor cell line-derived RNA reverses pancreatic tumor cell re sistance by directly triggering NK-like T lymphocytes.