Development of peptide vaccines for HLA-A24ィイD1+ィエD1 esophageal cancer patients.

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A main objective of this research project is to develop of peptide vaccines useful for HLA-A24ィイD1+ィエD1 patients with esophageal cancer. We have identified five tumor-rejection antigens (SART1-SART5) from cDNA esophageal cancer cells that were recognized by HLA-A24-restricted m derived from an esophageal cancer patient. SART-1, SART-2, and SART-3 tumor rejective antigens were newly identified molecules, while the remaining two were known molecules (Lck and PI9). SART-1, SART-2, SART-3, and PI9 tumor-rejection antigens were broadly expressed in the majority of esophageal cancers, while Lck was preferentially expressed in metastatic esophageal cancers. Peptide antigens recognized by the CTLs, and those capable of inducing HLA-class I restricted CTLs from peripheral blood mononuclear cells (PBMCs) of esophageal cancer patients were also identified in these tumor-rejection antigens. SART-1ィイD2690-698ィエD2 or SART-1ィイD2736-744ィエD2 peptide is currently used for phase I clinical studies as cancer vaccines in HLA-A24ィイD1+ィエD1 or -A26ィイD1+ィエD1 esophageal respectively, in our Kurume University Hospital. These basic and clinical research shall provide new insight for better understanding of molecular basis of T cell-mediated recognition of cancer cells. Further, these studies