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Idenification of tumor antigens in pancreatic cancer by proteomic analysis.

Research Project

Project/Area Number 15591461
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionThe 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)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
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)
KeywordsPancreatic 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 … More 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

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (18 results)

All 2004 2003 Other

All Journal Article (15 results) Publications (3 results)

  • [Journal Article] Immediate early response gene X-1, a stress-inducible antiapoptotic gene, encodes CTL epitopes capable of inducing HLA-A33-restricted and tumor-reactive CTLs in gastric cancer patients.2004

    • Author(s)
      Sasada T
    • Journal Title

      Cancer Research 64

      Pages: 2882-2888

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ran, A small GTPase gene, encodes CTL epitopes capable of inductiong HLA-A33-restricted and tumor-reactive CTLs in cancer patients.2004

    • Author(s)
      Azuma K
    • Journal Title

      Clinical Cancer Research 10

      Pages: 6695-6702

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Usefulness of 99mTc-sestamibi scintigraphy in suggesting the therapeutic effect of chemotherapy against gastric cancer.2004

    • Author(s)
      Kawata K
    • Journal Title

      Clinical Cancer Research 10

      Pages: 3788-3793

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Re : The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune mechanisms, and their association with prognostic indicators.2004

    • Author(s)
      Sasada T
    • Journal Title

      Surgery 136

      Pages: 1101-1101

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [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.
    • Journal Title

      Cancer Res. 64

      Pages: 2882-2888

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [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.
    • Journal Title

      Clin Cancer Res. 10

      Pages: 6695-6702

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Usefulness of 99 mTc-sestamibi scintigraphy in suggesting the therapeutic effect of chemotherapy against gastric cancer.2004

    • Author(s)
      Kawata K, Kanai M, Sasada T, Iwata S, Yamamoto N, Takabayashi A.
    • Journal Title

      Clin Cancer Res. 10

      Pages: 3788-3793

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Re : The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune mechanisms, and their association with prognostic indicators.2004

    • Author(s)
      Sasada T, Takabayashi A.
    • Journal Title

      Surgery. 136

      Pages: 1101-1101

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Immediate early response gene X-1, a stress-inducible antiapoptotic gene, encodes CTL epitopes capable of inducing HLA-A33-restricted and tumor-reactive CTLs in gastric cancer patients.2004

    • Author(s)
      Sasada T
    • Journal Title

      Cancer Resserch 64

      Pages: 2882-2888

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ran, a small GTPase gene, encodes CTL epitopes capable of inducing HLA-A33-restricted and tumor-reactive CTLs in cancer patients.2004

    • Author(s)
      Azuma K
    • Journal Title

      Clinical Cancer Research 10

      Pages: 6695-6702

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Re : The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune nechanisms, and their association with prognostic indicators.2004

    • Author(s)
      Sasada T
    • Journal Title

      Surgery 136

      Pages: 1101-1101

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies : possible involvement of regulatory T cells in disease progression.2003

    • Author(s)
      Sasada T
    • Journal Title

      Cancer 98

      Pages: 1089-1099

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Changes in mitochondrial membrane potential in peripheral blood lymphocytes, especially in natural killer cells, is a possible marker for surgical stress on the immune system.2003

    • Author(s)
      Takabayashi A
    • Journal Title

      World J Surg 27

      Pages: 659-665

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies : possible involvement of regulatory T cells in disease progression.2003

    • Author(s)
      Sasada T, Kimura M, Yoshida Y, Kanai M, Takabayashi A.
    • Journal Title

      Cancer. 98

      Pages: 1089-1099

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Change in mitochondrial membrane potential in peripheral blood lymphocytes, especially in natural killer cells, is a possible marker for surgical stress on the immune system.2003

    • Author(s)
      Takabayashi A, Kanai M, Kawai Y, Iwata S, Sasada T, Obama K, Taki Y.
    • Journal Title

      World J Surg. 27

      Pages: 659-665

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Tetsuro Sasada: "CD4^+CD25^+ regulatory T cells in patients with gastrointestinal malignancies : Possible involvement of regulatory T cells in disease progression."Cancer. 98. 1089-1099 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tetsuro Sasada: "Immediate early response gene X-1, a stress-inducible antiapoptotic gene. encoaes CTL epitopes capable of inducing HLA-A33-restricted and tumor-reactive CTLs in gastric cancer patients"Cancer Research. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Kenji Kawada: "Usefulness of 99mTc-MIBI scintigraphy in predicting the therapeutic effect of chemotherapy against gastric cancer."Clinical Cancer Research. (in press).

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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