| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
1.The aim of this project was to identify tumor-specific antigens that induce humoral responses in pancreatic cancer patients by proteomic approach. Aliquots of solubilized proteins from pancreatic cancer cell lines were subjected to two-dimensional PAGE, followed by Western blot analysis with sera from 5 pancreatic cancer patients and 5 healthy subjects. The spots detected only in cancer patients were analyzed by mass spectrometry to identify the antigens recognized by tumor-specific autoantibodies. Unfortunately, although I tried several experimental conditions, I could not get valid and reproducible results by this approach. Therefore, I decided to modify the approach. Briefly, aliquots of solubilized proteins from cancer cell lines were subjected to immunoprecipitation with autoantibodies purified from pancreatic cancer patients and healthy subjects, followed by two-dimensional PAGE and mass spectrometry. Work is now in progress to identify novel tumor antigens that could be potent
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candidates for specific immunotherapy against pancreatic cancer patients.
2.Peptide-based vaccine therapy, which is designed to elicit T-cell immunity against tumors, is an attractive approach for the treatment of cancer patients. We tried to identify CTL-directed peptides for antigen-specific immunotherapy. 850B-CTLs, HLA-A33-restricted CTLs, were newly established from T cells infiltrating into gastric adenocarcinoma. By expression-cloning technique, two proteins, IEX-1 and Ran, were identified as tumor-specific antigens which were specifically recognized by the 850B-CTL. Both proteins are suggested to be involved in the proliferation of cancer cells and highly expressed in most cancer cell lines and tissues. Peptides derived from IEX-1 or Ran, which were recognized by the 850B-CTLs, could induce CD8^+ peptide-specific CTL reaction to tumor cells from HLA-A33^+ gastric cancer patients and other epithelial cancer patients, but not from healthy donors, in an HLA class I-restricted manner. These antigenic peptides could be potent candidates for peptide-based specific immunotherapy against HLA-A33^+ gastric cancer and other epithelial cancers. Less
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