|Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
We assessed the inducibility of peptide-specific CTL by DC derived from healthy donors, patients with chronic hepatitis, or with hepatoma who had HLA-A2 or/and A24. Seven healthy donors, six chronic hepatitis C virus patients, and six with hepatoma were enrolled. In healthy donors and patients with chronic hepatitis, peptide-specific CTL was comparably induced but not in all of six patients with HCV-positive HCC. To further characterize this phenomenon, 1) the pattern cytokine released in CTL induction, 2) the expression of the cell surface molecule involving in the signaling interaction between DC and T cells, and 3) the genotype of.HLA-A2 /A24 were evaluated. Production of IFN-y was found to be impaired, and the genotype of HLA-A2 and -A24 were crucial of inducing CTL with peptide, while the expression of cell surface molecules involving in signaling of DC to T cells showed no significant difference. These findings indicate poor feasibility of peptide vaccine against HCV-positive HCC patients. To overcome this limited situation, such as HLA genotype and the epitope information, we tried to develop a new approach of the immunotherapy, that is poly (iactide-co-glycolide) microparticle (PLGA) engulfed various expression vectors as new delivery system of indicated genes into DC. So far it is confirmed that DCs phagocytize PLGA containing the gene, express an indicated protein, released cytokines in the interaction with T cells, and induce CTL specific to HCV core protein. In the future, we will confirm that this method is effective in patients with HCV-positive HCC and that the possibility of cocktail therapy mixing several genes and the feasibility of applying to human body are explored.