ACTIVE SPECIFIC IMMUNE-INDUCTION BY TUMOR-ANTIGEN DERIVED-PEPTIDE RECOGNIZED BY T CELLS

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We have investigated the expression of genes of MAGE-1, MAGE-3 and HLA-A1 for 10 breast cancer, 31 esophgeal cancer and 4 pancreatic cancer patients. There was no patint who had HLA-A1. The expression of MAGE-1 and MAGE-3 was one out of ten (10%) and 3 (30%), in breast cancer patients, respectively. In esophageal cancer patients, 7 out of 31 (23%) expressed MAGE-1 and 14 (47%) did MAGE-3, while 3 (10%) had both MAGE-1 and MAGE-3. In pancreatic cancer, 1 out of 4 (25%) expressed MAGE-1 and 2 (50%) showed MAGE-3, one (25%) had both MAGE-1 and MAGE-3. These gene expression was confirmed to be translated into the corresponding protein by Western blot analysis except for one breast cancer. Survival of those esophageal cancer patients whose tumor expressed both MAGE-1 and MAGE-3 were significantly better than that of other patients. In preparation for clinical application of active specific immunotherapy, we made experiments using materials from a esophageal cancer patient who is HLA-A2 positive and whose tumor expressed MAGE-3. The patint's peripheral blood lymphocytes proliferated significantly when they were stimulated with HLA-A2 restriced MAGE-3-derived-pepitde-pulsed cultured dendritic cells while they did not proliferate in the presence of HLA-A1 restriced peptide-pulsed dentritic cells. The appropriately stimulated lymphocytes produced tumor necrotizing factor. Finally, those lymphocytes showed significant cytotoxicity against HLA-A2&MAGE-3 positive autologous cancer cell line and had less cytotoxicity against HLA-A24/MAGE-3 positive allogeneic cell line. These results clearly show the potentiality of clinical application of peptide based tumor immunotherapy using professional antigen presenting cells. To identify the repertoire of T cell receptor in this system in under progress by lymphocyte cloning.