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

Research Project

Project/Area Number 12671282
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKurume University

Principal Investigator

YAMANA Hideaki  Kurume University, Medicine, Professor, 医学部, 教授 (30140669)

Co-Investigator(Kenkyū-buntansha) SHICHIJO Shigeki  Kurume University, Medicine, Associate Professor, 医学部, 助教授 (30080592)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsadbanced esophageal canser / HLA class I-restriction / sutologous activated lymphocytes / cancer rejection antigen gene / killer T cell precursor / cancer peptide vaccine / Phase I cinical trial / Immunomonitoring / 高度進行食道癌 / 癌特異的キラーT細胞 / HLA class I 拘束性 / キラーT前駆細胞 / 細胞性免疫評価
Research Abstract

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.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Inoue Y: "Induction of human leukocyte antigen-A26-restricted and tumor-specific cytotoxic T lymphocytes by a single peptide of the SART1 antigen in patients with cancer with different A26 subtypes"J.Immunotherapy.. 23・3. 269-303 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toh U: "Locoregional cellular immunotherapy for patients with advanced esophageal cancer"Clin.Cancer.Res.. 6. 4663-4673 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakao M: "Identification of a gene coding for a new squamous cell carcinoma antigen recognized by the CTL"J.Immunol.. 164. 2565-2574 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niiya F: "Expression of SART3 tumor-rejection antigen in gastric cancers"Jpn.J.Cancer.Res. 91. 337-342 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toh U: "Specific adoptive immunotherapy with autologous tumor cell-activated lymphocytes for esophageal cancer"Biotherapy.. 14・1. 26-28 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyagi Y: "Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination with SART3 peptides"Clin.Cancer.Res.. 7・12. 3950-3962 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue Y: "Induction of human leukocyte antigen-A26-restricted and tumor-specific cytotoxic T lymphocytes by a single peptide of the SART1 antigen in patients. with cancer with different A26 subtypes."J Immunotherapy. 23(3). 269-303 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toh U: "Locoregional cellular inununotherapy for patients with advanced esophageal cancer."Clin Cancer Res. 6. 4663-4673 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakao M: "ldentification of a gene coding for a new squamous cell carcinoma antigen recognized by the CTL."J Immunol. 164. 2565-2574 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niiya F: "Expression of SART3 tumor-rejection antigen in gastric cancers."Jpn J Cancer Res. 91. 337-342 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toh U: "Specific adoptive inununotherapv with autologous tumor cell-activated lymphocytes for esophageal cancer."Biotherapy. 14(1). 26-28 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sasatomi T: "Expression of the SART1 tumor rejection antigens in colorectal cancers."Dis Colon Rectum. 43(12). 1754-1758 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Harashima N: "Recognition of the Ick tyrosine kinase as a tumor antigen by cutotoxic T lymphocytes of cancer patients with distant metastasis,"Eur J Immunol. 31. 323-332 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyagi Y: "Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination with SART3 peptides,"Clin Cancer Res. 7(12). 3950-3962 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii T: "Expression of G1 cell cycle markers and the ffect of adenovirus mediated overexpression of p21 Waf-1 in squamous cell carcinoma of the esophagus"Int J Oncol. 18・1. 157-163 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Harashima N: "Recognition of the lck tyrosine kinase as a tumor antigen by cutotoxic T lymphocytes of cancer patients with distant metastasis"Eur J Immunol. 31. 323-332 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagamatsu Y: "Preoperative evaluation of cardiopulmonary reserve with the use of expired gas analysis during exercise testing with squamous cell carcinoma of the esophagus"J Thorac Crdiovasc Surg. 121・6. 1064-1068 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Imamura M: "Prognostic significance of cyclinD1 and E-cadherin in patients with esophageal squamous cell carcinoma : multiinstitutional retrospective analysis"J Am Coll Surg. 192・6. 708-718 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi K: "Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus"Jpn J Clin Oncol. 31・9. 419-423 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kihara C: "Prediction of sensitivity of esophageal tumors to adjuvant chemo-therapy by cDNA microarray analysis of gene-espression profiles"Cancer Res. 61・9. 6474-6479 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ide H: "Recent Advances in Diseases of the Esophagus"Comprehensive registry of esophageal cancer in Japan from 1988 to 1994. 385 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 山名秀明: "扁平上皮癌抗原SARTを標的とした免疫療法"血液・免疫・腫瘍. 5・2. 167-172 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 山名秀明: "進行食道癌に対する免疫療法"消化器外科. 23・6. 1029-1036 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 山名秀明: "Immunoguided Surgery"日本外科学会雑誌. 101・9. 602-606 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 山名秀明: "癌ワクチン"癌と化学療法. 27・10. 1477-1488 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masanobu Nakao: "Identification of a gene coding for a new squamous cell carcinoma antigen recognized by the CTL"Journal of Immunology. 164・5. 2565-2574 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Uhi Toh: "Locoregional cellular immunotherapy for patients with advanced esophageal cancer"Clinical Cancer Research. 6・12. 4663-4673 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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