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Clinical application and development of DNA vaccine gene immunotherapy targeting MUC1 as tumor antigen

Research Project

Project/Area Number 16591392
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionShiga University of Medical Science

Principal Investigator

TAZUKA Noriaki  Shiga University of Medical Science, Department of Surgery, Assistant Professor, 医学部, 助手 (40303771)

Co-Investigator(Kenkyū-buntansha) SAWAI Satoru  Shiga University of Medical Science, Department of Surgery, Assistant Professor, 医学部, 助手 (60335172)
FUJINO Shozo  Shiga University of Medical Science, Department of Surgery, Associate Professor, 医学部, 助教授 (10209075)
OZAKI Yoshitomo  Shiga University of Medical Science, Department of Surgery, Assistant Professor, 医学部, 助手 (00378449)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsDNA vaccine / tumor immunotherapy / cytotoxic T cell / helper T cell / MUC1 / 細胞傷害性T細胞
Research Abstract

Objective. MUC1 DNA vaccine immunotherapy must induce helper and cytotoxic cell-mediated immunity to generate the powerful anti-tumor immune responses needed to suppress cancer progression. We pay attention to MHC class II peptide (Pan-I a peptide) efficiently stimulated T-helper 1 type lymphocytes which was prepared from the pigeon cytochrome c. We investigated whether co-administration of DNA vaccine and dendritic cells pulsed with Pan-I a peptide (DC-IA) can elicit various immunological mechanism and lead to enhancement of anti-tumor immunity in murine model.
Results. At first instead of MUC1 we used OVA as tumor antigen, C57BL/6 mice were given an injection of DNA encoding OVA (OVA DNA), and we assayed. 1. OVA DNA vaccines could not suppress tumor growth in mice inoculated with E.G7 generated by transducing the chicken OVA gene into EL4 cells. 2. Although the OVA DNA vaccine elicited significant anti-OVA immunity compared with Mock DNA, there was no difference of cytotoxicity against E.G7 between OVA DNA and Mock DNA. 3. Co-administration of OVA DNA and DC-IA elicited tumor specific cytotoxicity, and suppuresive effects on tumor growth in tumor bearing mouse. 4. Tumor infiltrating IFN-γ producing CD4 or CD8 positive cells were significantly increased in mouse bearing E.G7 tumors by vaccination of OVA DNA and DC-IA compared with that in other groups of mice.
Conclusion. Co-administration of DNA vaccine and dendritic cells pulsed with Pan-I a peptide (DC-IA) augemented anti-tumor effects. Now we are investigating this murine model replacing OVA and Pan-I a peptide with MUC1 and Pan-DR peptide (PADRE) that can be presented by various types of mouse and human MHC class II molecules.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (6 results)

All 2006 2004

All Journal Article (6 results)

  • [Journal Article] Successful tumor eradication was achieved by corroboration of augmented cytotoxic activity and anti-angiogenic effects following therapeutic vaccines containing helper activating analogue loaded dendritic cells and tumor antigen DNA.2006

    • Author(s)
      Koji Teramoto, et al.
    • Journal Title

      Cancer Immunol Immunother (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Successful tumor eradication was achieved by corroboration of augmented cytotoxic activity and anti-angiogenic effects following therapeutic vaccines containing helper activating analogue loaded dendritic cells and tumor antigen DNA.2006

    • Author(s)
      Koji Teramoto, et al.
    • Journal Title

      Cancer Immunol Immunother. in press

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of 90K/Mac-2 binding protein in cancer metastases by increased cellular adhesiveness in lung cancer.2004

    • Author(s)
      Ozaki Y., et al.
    • Journal Title

      Oncology Report. 12(5)

      Pages: 1071-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of antigenic epitopes recognized by Mac-2 binding protein-specific cytotoxic T lymphocytes for use in cancer immunotherapy.2004

    • Author(s)
      Ozaki Y., et al.
    • Journal Title

      Biochem Biophys Res Commun. 317(4)

      Pages: 1089-95

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of 90K/Mac-2 binding protein in cancer metastases by increased cellular adhesiveness in lung cancer.2004

    • Author(s)
      Ozaki Y, et al.
    • Journal Title

      Oncol Rep. 12(5)

      Pages: 1071-1077

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of antigenic epitopes recognized by Mac-2 binding protein-specific cytotoxic T lymphocytes for use in cancer immunotherapy.2004

    • Author(s)
      Ozaki Y., et al.
    • Journal Title

      Biochem Biophys Res Commun. 14 ; 317(4)

      Pages: 1089-1095

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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