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A novel cancer immunotherapy with down-regulation of regulatory T cells using pretreatment of mild bone marrow suppression.

Research Project

Project/Area Number 18591474
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

ITOH Tsuyoshi  Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Assistant Professor (40420707)

Co-Investigator(Kenkyū-buntansha) YAMAGISHI Hisakazu  Kyoto Prefectural University of Medicine, President (40128723)
上田 祐二  京都府立医科大学, 医学研究科, 講師 (60254356)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥2,040,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsColorectal Surgery / Cancer vaccine
Research Abstract

(1) An effect of mild immunosuppression was observed in mice administered cyclophosphamide. Cytotoxic T lymphocyte (CTL) response was enhanced in mice with this pretreatment possibly due to the down regulation of regulatory T cells which is considered to drive T helper-2 (112) immune response.
(2) The administration of anti-CD40 ligand monoclonal antibody (mAb) augmented this CTL response.
(3) Cancer vaccine protocol using the pretreatment of cyclophosphamide and the administration of a CD40L was evaluated as for its CTL response as well as anti tumor effect. C57B1/6 mice immunized with S11NFEKT peptide using this vaccine protocol were challenged with B16-0UA tumor cell lines. An enhancement of peptide-specific CTL response and anti tumor effect was observed. Its anti tumor effect was strongest in mice immunized with peptide concomitantly given cyclophosphamide and a-CD4OL Although some response was demonstrated in mice immunized with peptide alone, cyclophosphamide and a-CD40L elicited more strong peptide specific CM response and rejected tumor challenged after vaccination.
In conclusion, pretreatment of cyclophophamide and a-CD40L aiming at the down regulation of regulatory T cells enhanced peptide specific T cell response and effectively elicited anti tumor response. This vaccine protocol may be the break through for optimal cancer vaccine therapy.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (23 results)

All 2008 2007 2006

All Journal Article (19 results) (of which Peer Reviewed: 8 results) Presentation (4 results)

  • [Journal Article] Port site herniation of the small bowel following laparoscopy-assisted distal gastrectomy:a case report2008

    • Author(s)
      Itoh T, Fuji N, Taniguchi H, ら
    • Journal Title

      Journal of medical case reports 2

      Pages: 48-50

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Port site herniation of the small bowel following laparoscopy-assisted distal gastrectomy : a case report2008

    • Author(s)
      Itoh, T
    • Journal Title

      Journal of medical case reports 2

      Pages: 48-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Port site herniation of the small bowel following laparoscopy-assisted distal gastrectomy: a case report.2008

    • Author(s)
      Itoh T, Fuji N, Taniguchi H, ら
    • Journal Title

      Journal of medical case reports 2

      Pages: 48-50

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fli3 ligand promotes myeloid dendritic cell differentiation of human hematopoietic progenitor cells:possible application for cancer immunotherapy2007

    • Author(s)
      Harada S, Kimura T, Fujiki H, Nakagawa H, Ueda Y, ltoh T, Yamagishi H, Sonoda Y
    • Journal Title

      International Journal of Oncology 6

      Pages: 1461-1468

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Induction of peptide-specific immune response in patients with primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides2007

    • Author(s)
      Ueda Y, Shimizu K, Itoh T, ら
    • Journal Title

      Japanese Journal of Clinical Oncology 2

      Pages: 140-145

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Successful induction of clinically competent dendritic cells from granulocvte colony-stimulating factor-mobilized monocvtes for cancer vaccine therapy2007

    • Author(s)
      Ueda Y, Itoh T, Fuli N, et. al.
    • Journal Title

      Cancer Immunology Immunotherapy 56(3)

      Pages: 381-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] F1t3 ligand promotes myeloid dendritic cells differentiation of Human hematopoietic progenitor cells: possible application for cancer Immunotherapy.2007

    • Author(s)
      Harada, S
    • Journal Title

      International Journal of Oncology 6

      Pages: 1461-1468

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Induction of peptide-specific immune response in patients with Primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides.2007

    • Author(s)
      Ueda, Y
    • Journal Title

      Japanese Journal of Clinical Oncology 2

      Pages: 140-145

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Successful induction of clinically competent dendritic cells from Granulocyte colony-stimulating factor-mobilized monocytes for cancer vaccine therapy.2007

    • Author(s)
      Ueda, Y
    • Journal Title

      Cancer Immunology Immunotherapy 56

      Pages: 381-389

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Fli3 ligand promotes myeloid dendritic cell differentiation of human hematopoietic progenitor cells: possible application for cancer immunotherapy.2007

    • Author(s)
      Harada S, Kimura T, Fujiki H, Nakagawa H, Ueda Y, Itoh T, Yamagishi H, Sonoda Y
    • Journal Title

      International Journal of Oncology 6

      Pages: 1461-1468

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of peptide-specific immune response in patients with primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides.2007

    • Author(s)
      Ueda Y, Shimizu K, Itoh T, ら
    • Journal Title

      Japanese Journal of Clinical Oncology 2

      Pages: 140-145

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of peptide-specific immune response in patients with Primary malignant melanoma of the esophagus after immunotherapy using Dendritic cells pulsed with MAGE peptides.2007

    • Author(s)
      Ueda Y, Shimizu K, Itoh T, et al.
    • Journal Title

      Japanese Journal of Clinical Oncology 37(2)

      Pages: 140-5

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Successful induction of clinically competent dendritic cells from granulocyte colony-stimulating factor-mobilized monocytes for cancer vaccine therapy.2007

    • Author(s)
      Ueda Y, Itoh T, Fuji N, et al.
    • Journal Title

      Cancer Immunology Immunotherapy 56(3)

      Pages: 381-9

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A new strategy using autologous dendritic cells and lymphokine-activated killer cells for cancer immunotheraPy:efficient maturation of DCs by co-culture with LAk cells in vitro2006

    • Author(s)
      Yano Y, Ueda Y, Itoh T, et. al.
    • Journal Title

      Oncology Report 16(1)

      Pages: 1481-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Mature dendritic cells generated from patient-derived peripheral blood monocvtes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity2006

    • Author(s)
      Naito K, Ueda Y, Itoh T, et. al.
    • Journal Title

      International Journal of Oncology 28(6)

      Pages: 1481-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A new strategy using autologous dendritic cells and Lymphokine-activated killer cells for cancer immunotherapy: efficient Maturation of DCs by co-culture with LAK cells in vitro.2006

    • Author(s)
      Yano, Y
    • Journal Title

      Oncology Report 16

      Pages: 1481-1489

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity.2006

    • Author(s)
      Naito, K
    • Journal Title

      International Journal of Oncology 28

      Pages: 1481-1489

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A new strategy using autologous dendritic cells and Iymphokine-activated killer cells for cancer immunotherapy : efficient maturation of DCs by co-culture with LAK cells in vitro.2006

    • Author(s)
      Yano Y, Ueda Y, Itoh T, et al.
    • Journal Title

      Oncology Report 16(1)

      Pages: 147-52

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity.2006

    • Author(s)
      Naito K, Ueda Y, Itoh T, et al.
    • Journal Title

      International Journal of Oncology 28(6)

      Pages: 1481-9

    • Related Report
      2006 Annual Research Report
  • [Presentation] Outcomes of supervised surgical training for the resection of colo-rectal cancer2007

    • Author(s)
      Itoh T, Fuji N, et. al.
    • Organizer
      93rd annual clinical congress of American College of Surgeons
    • Place of Presentation
      New Orleans USA
    • Year and Date
      2007-10-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Outcomes of supervised surgical training for the resection of colo-rectal cancer2007

    • Author(s)
      Itoh, T
    • Organizer
      93rd annual clinical congress of American College of Surgeons
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2007-10-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Successful induction of clinically competent dendritic cells from franurocyte colony-stimulating factor-mobilized monocytes for cancer vaccine therapy2006

    • Author(s)
      伊藤 剛, 上田 祐二, 山岸 久一, ら
    • Organizer
      日本バイオセラピー学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2006-11-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Successful induction of clinically competent dendritic cells from glanulocyte colony-stimulating factor-mobilized monocytes for cancer vaccine therapy2006

    • Author(s)
      Itoh, T
    • Organizer
      Biotherapy society meeting
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2006-11-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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