OBJECTIVETo investigate the effects of dendritic cells (DCs) infected with adenovirus vector encoding xenogeneic alpha-fetoprotein (AFP) on breaking the immune tolerance and induction of immunity against hepatocellular carcinomas.

METHODSHuman and mouse alpha-fetoprotein full-length cDNA were cloned from human HepG2 and mouse Hepa 1 - 6 hepatoma cell lines, respectively, using RT-PCR, and then inserted into adenoviral shuttle vectors to construct Ad hAFP and Ad mAFP. Mice were immunized with Ad hAFP-infected DC and in vitro CTL activity against Hepa 1 - 6 cells was examined by standard (51)Cr release assay. Survival was studied of the immunized mice, with or without depletion of CD8+ or CD4+ T cells, inoculated with Hepa 1 - 6 mouse hepatoma cells.

RESULTSThe lytic activity of CTL elicited by the Ad hAFP-infected DCs were much stronger than that by Ad mAFP-infected DCs. 80% of the Ad hAFP/DCs-immunized mice of the inoculated with 5 x 10(6) Hepa 1 - 6 hepatoma cells were still alive two months after inoculation. However, the Ad mAFP/DCs-immunized mice inoculated with 1 x 10(6) Hepa 1 - 6 cells were just 20% surviving two months later. Depletion of CD8+ or CD4+ T cells abolished such an antigen-specific immunity elicited by the DCs infected with Ad hAFP.

CONCLUSIONAdenovirus vector-mediated xenogeneic AFP-infected DCs can effectively break the immune tolerance to hepatocellular carcinomas in an animal model and induce strong antigen-specific T cell response, which are dependent on CD8+ and CD4+ T cells.