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2003 Fiscal Year Final Research Report Summary

Immunotherapy of hematological melignancies based on activation of innate immunity and costimulation through OX40/OX40L

Research Project

Project/Area Number 14207041
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

UCHIYAMA Takashi  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (80151900)

Co-Investigator(Kenkyū-buntansha) HORI Toshiyuki  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (70243102)
KADOWAKI Norimitsu  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (60324620)
Project Period (FY) 2002 – 2003
Keywordsinnate immunity / ONO-4007 / OX40 / OX40 ligand / fumor vaccine / anti-fumor immunity
Research Abstract

In the present study, we attempted to develop novel immune therapeutic modalities against hematological melignancies based on activation of innate immunity and costimulation through OX40/OX40L..
A LPS-derived compound, ONO-4007, was enclosed in liposomes and injected to C57/B6 mice that had been preinoculated with EL4, a mouse T cell lymphoma cell line. The tumor was infiltrated with neutrophils after 24 h and showed necrotic change after 72 h. However, we could not detect significant difference between liposome-enclosed and non-enclosed ONO-4007.
Fresh leukemic cells from 5 AML patients were cultured with SCF, Flt3-L, GM-CSF, and TNF-α to differentiate into dendritic cell (DC)-like cells. At the same time, a part of cultured leukemic cells were retrovirally transduced with OX40L or mock control. We showed that OX40L-transduced leukemia-DC had the highest capacity to induce proliferation and IFN-g production of allogeneic CD-4+ T cells.
C57BL/6 mice were inoculated with 1×10^5 cells of parental EL4, OX40L-transfected EL4 (EL4-OX40L), or mock control vector-transfected EL4 (EL4-mock). While both parental EL4 and EL4-mock grew rapidly, EL4-OX40L was rejected or grew slower than parental EL4 or EL4-mock. In vitro CTL assay demonstrated that spleen cells of mice that had rejected EL4-OX40L had significant cytotoxic activity against parental EL4.
In conclusion, activation of innate immunity was demonstrated to be efficacious to eradicate tumors, and the gene transfer of OX40L into lymphoma cells is an eligible and efficient modality to induce anti-lymphoma immunity.

  • Research Products

    (11 results)

All 2004 2003 Other

All Journal Article (11 results)

  • [Journal Article] Retroviral transduction of acute myeloid leukemia-derived dendritic cells with OX40 ligand augments their antigen presenting activity.2004

    • Author(s)
      Soshi Yanagita et al.
    • Journal Title

      Br.J.Haematol. 124

      Pages: 454-462

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Depletion and impaired interferon-α-producing capacity of blood plasmacytoid dendritic cells in human T-cell leukemia virus type I(HTLV-I)-infected individuals.2004

    • Author(s)
      Masakatsu Hishizawa et al.
    • Journal Title

      Br.J.Haematol. 125

      Pages: 568-575

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Retroviral transduction of acute myeloid leukemia-derived dendritic cells with OX40 ligand augments their antigen presenting activity.2004

    • Author(s)
      Soshi Yanagita
    • Journal Title

      Br.J.Haematol. 124

      Pages: 454-462

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Depletion and impaired interferon-α-producing capacity 1. of blood plasmacytoid dendritic cells in human T-cell leukaemia virus type I (HTLV-I)-infected individuals.2004

    • Author(s)
      Masakatsu Hishizawa
    • Journal Title

      Br.J.Haematol. 125

      Pages: 568-575

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Immunotherapy exploiting the versatility of dendritic cells.2003

    • Author(s)
      Norimitsu Kadowaki
    • Journal Title

      Therapeutics Apheresis and Dialysis 7

      Pages: 312-317

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Compromised recovery of natural interferon-alpha/beta-producing cells after allogeneic hematopoietic stem cell transplantation complicated by acute graft-versus-host disease and glucocorticoid administration.2003

    • Author(s)
      Toshio Kitawaki et al.
    • Journal Title

      Bone Marrow Transplant 32

      Pages: 187-194

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] OX40 signaling is crucial for induction of alloreactive human T cell response.2003

    • Author(s)
      Naoya Ukyo et al.
    • Journal Title

      Immunology 109

      Pages: 226-231

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Compromised recovery of natural interferon-alpha/beta-producing cells after allogeneic hematopoietic stem cell transplantation complicated by acute graft-versus-host disease and glucocorticoid administration2003

    • Author(s)
      Toshio Kitawaki
    • Journal Title

      Bone Marrow Transplant 32

      Pages: 187-194

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] OX40 signaling is crucial for induction of alloreactive human T cell response.2003

    • Author(s)
      Naoya Ukyo
    • Journal Title

      Immunology 109

      Pages: 226-231

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo.

    • Author(s)
      Hitomi Kaneko et al.
    • Journal Title

      Exp.Hematol. in press

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo.

    • Author(s)
      Hitomi Kaneko
    • Journal Title

      Exp.Hematol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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