|Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
We have clarified that tumor-rejection antigens such as MAGE-1, MAGE-3 and NY-ESO-1 are expressed in a significant proportion of human hepatocellular carcinoma(HCC)at mRNA and protein levels. These genes are not expressed normal somatic cells except for testis. Although we have attempted to detect cytotoxic T-cell responses against MAGE-3 or NY-ESO-1 derived peplides in HLA-A2 positive healthy volunteers and HCC patients, we could not detect it to date. Since it has been reported that CTL activity against NY-ESO-1 was detected in melanoma patients in whom IgG antibodies against NY-ESO-1 was found in serum, we have also tried to detect serum antibodies in HCC patients. As a result, the IgG antibodies were observed in two of 100 patients with HCC.This result suggests that immune response against NY-ESO-1 is developed in HCC patients and NY-ESO-1 derived peptides can be used for vaccine therapy in HCC patients. In contrast, we have analyzed the expression of antigen-processing and antigen-presenting molecules, e.g., LMP-2, -7, Heat shock protein, TAP, β2-microglobulin, HLA class-I and B7-1 and -2. We have clarified that the expression of co-stimulatory molecules, B7-1 and -2 was lost in a significant proportion of HCC and that of HLA class-I molecule was also reduced in less frequency. These results indicate that HCC escape from immune surveillance via the losses of these molecules especially via the loss of B7 molecules. For the next step for immunotherapy in HCC patients, we have to determine whether the transfection of B7 molecules in dendritic cells as APC or HCC cells as the target cells can elicit CTL responses against tumor-rejection antigens. Further, we have carried out SEREX and identified four molecules are aberrantly expressed in HCC.We are also examining the expression of OY-TES-1 gene in human HCC samples, which was discovered as one of cancer-testis antigens in our university.