2004 Fiscal Year Final Research Report Summary
Idenification of tumor antigens in pancreatic cancer by proteomic analysis.
Project/Area Number |
15591461
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | The Tazuke Kofukai |
Principal Investigator |
SASADA Tetsuro The Tazuke Kofukai, Medical Research Institute, Second Department, Chief Researcher, 医学研究所・第2研究部, 主任研究員 (70293967)
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Project Period (FY) |
2003 – 2004
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Keywords | Pancreatic cancer / Proteome / Tumor antigen |
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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Research Products
(12 results)
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[Journal Article] Immediate early response gene X-1, a stress-inducible antiapoptotic gene, encodes cytotoxic T-lymphocyte (CTL) epitopes capable of inducing human leukocyte antigen-A33-restricted and tumor-reactive CTLs in gastric cancer patients.2004
Author(s)
Sasada T, Takedatsu H, Azuma K, Koga M, Maeda Y, Shichijo S, Shoumura H, Hirai T, Takabayashi A, Itoh K.
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Journal Title
Cancer Res. 64
Pages: 2882-2888
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ran, a small GTPase gene, encodes cytotoxic T lymphocyte (CTL) epitopes capable of inducing HLA-A33-restricted and tumor-reactive CTLs in cancer patients.2004
Author(s)
Azuma K, Sasada T, Takedatsu H, Shomura H, Koga M, Maeda Y, Yao A, Hirai T, Takabayashi A, Shichijo S, Itoh K.
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Journal Title
Clin Cancer Res. 10
Pages: 6695-6702
Description
「研究成果報告書概要(欧文)」より
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