INDUCTION OF PRIMARY CARCINOEMBRYONIC ANTIGEN (CEA)-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN-VITRO USING HUMAN DENDRITIC CELLS TRANSFECTED WITH RNA

Dendritic cells (DC) generated from the peripheral blood mononuclear c ells of healthy individuals or from cancer patients transfected with c arcinoembryonic antigen (CEA) mRNA stimulate a potent CD8(+) cytotoxic T lymphocyte (CTL) response in vitro. DCs are effectively sensitized with RNA in the absence of reagents commonly used to facilitate mammal ian cell transfection. RNA encoding a chimeric CEA/LAMP-1 lysosomal ta rgeting signal enhances the induction of CEA-specific CD4(+) T cells, providing a strategy to induce T-hel that may be necessary to generate and/or maintain an optimal CD8(+) CTL response in vivo, CEA RNA-trans fected DCs also serve as effective targets in cytotoxicity assays, thu s providing a general method for inducing, as well as measuring, CEA-s pecific CTL responses across a broad spectrum of HLA haplotypes.