Fundamental and clinical research for esophageal cancer rejection peptide antigens as a vaccine therapy

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We investigated the existence of cancer specific cytotoxic T lymphocytes (CTLs) against cancer cells in peripheral blood. Peripheral blood mononuclear cells (PBMC) sampled from advanced cancer patients were cultured with an addition of IL-2 (100U/ml) for about 14 days. Following the cultivation, predominant CTLs including NK cells and LAK cells were recognized in PBMC collected from many patients with advanced esophageal cancer. These CTLs expressed CD4 negative and CD8 positive. Using the CTL, new cancer rejection antigen gene was examined by expression cloning method presented by Boon in 1991.We found a new cancer rejection gene of MRP3 that connected to HLA-A24 molecule. MRP is well known as a multi drug resistant protein and usually many malignant cells express this protein. Therefore MRP3 peptide seems to be useful as a cancer vaccine.We performed a new clinical phase I trial for advanced or recurrent cancer patients using CTL precursor-oriented cancer vaccine method. To define the effective peptide vaccines prior to treatment, patients PBMC was examined by a stimulation of 14-cancer vaccine in vitro. hrimimoreaction was examined in vitro by a newly created method evaluating the concentration of IFN-gamma production that needs about 2 weeks. In the Phase I trial using 14 cancer vaccines, CTL precursor of many cases was increased but no clinical effect was found in patients with far advanced esophageal carcinoma due to severe progression of the cancer. This clinical result was also found in patients with advanced pancreatic cancer or gastric cancer. For the next study of cancer vaccine, we have to investigate about more effective adjuvant and/or combined therapy against esophageal carcinoma.