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Differentiation of dendritic cells and their use for tumor immunology

Research Project

Project/Area Number 09671119
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OTSUKA Teruhisa  Kyushu University, Medicine, Assistant Professor, 医学部, 講師 (20185317)

Co-Investigator(Kenkyū-buntansha) ITOH Yoshikiyo  Kyushu University, Medicine, Medical Stuff, 医学部, 医員
SUGIO Yasuhiro  Kyushu University, Medicine, Medical Stuff, 医学部, 医員
MAEDA Motoi  Kyushu University, Medicine, Medical Stuff, 医学部, 医員
IINO Tadafumi  Kyushu University, Medicine, Medical Stuff, 医学部, 医員
内田 直之  九州大学, 医学部, 医員
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsdendritic cell / tumor immunology / AML1 / MTG8 / cytotoxic T-cell / クリオグロブリン血症 / HLA拘束性 / 慢性骨髄性白血病
Research Abstract

We succeeded to generate dendritic cells from adherent peripheral blood mononuclear cells cultured with rhGM-CSF, rhIL-4 and rhTNF-alfa. After 10days, the cultured cells, which display the typical cell surface markers of mature monocyto-derived dendritic cells (Mp-DCs) and induce T cells to make primary and secondary immune response are harvested. Then, we tried to identify the tumor antigen of acute leukemia using Mo-DCs. We made the hypothesis that the overexpression of the MTG8 gene in t (8 ; 21) AML cells could act as a possible tumor antigen, which might be able to induce the immune-mediated suppression of the expansion of MRD. We were able to induce HLA-A0201-restricted cytotoxic T-lymphocyte (CTL) lines against an MTG8 peptide (MTG8b aa182-191) using Mo-DCs from a healthy donor. T cell receptor (TCR) Vα17, TCRVβ14 and 15, and TCRJβ2.1 and 2.3 are predominantly used in these CTL lines. Our data which suggest that the MTG8 protein could be one of the tumor antigens recognized by CTLs may be helpful in further investigations of TCR analysis in t (8 ; 21) AML patients with HLA-A0201 who are in long-term remission. Finally, we vaccinated a refractory essential monoclonal cryoglobulinemia patient with Mo-DCs pulsed with purified cryoglobulin as a tumor antigen. During the vaccinations, his acrocyanosis improved and we were able to reduce the number of hot baths used to treat his symptoms, with no side effect. Furthermore, cryoglobulin-specific proliferative responses were observed after the vaccination. As there was a recurrence of acrocyanosis after the final vaccination, vaccination with Mo-DCs pulsed with purified cryoglobulin would seem to be a useful treatment for refractory essential monoclonal cryoglobulinemia.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Maeda M, et al: "Introduction of the MTG8 specificcytotoxic T-cell lines: possibility of MTG8 as a umorantigen recognized by cytotoxic T-cells in AML 1/MTG8 fused gened positive acutemyelogenous leukemia"Cancer Res:. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maeda M, et al: "Vaccination of cryoglobulinemia patient with cryoglobulin pulsed monocyte-derived dendritic cells."Leukemia Lymphoma:. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Otsuka T, et al: "Human telomeric protein TRF1 gene expression is downregulated during myeloid differentiation in human hematopoietic cells."Int J Hematol:. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukuyama T, et al: "Profliferative involvement of ENX-1, a putative human polycomb group gene, in haematopoietic cells."Brit J Haematol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uchida N, et al: "Correlation of telomerase activity with development and progression of adult T-cell leukemia."Leuk Res. 23. 311-316 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uchida N, et al: "Differential gene expression of human telomerase-associated protein Htert and TEP1 in human hematopoietic cells."Leuk Res. 23. 1127-1132 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maeda M. et al.: "Induction of the MTG8 specific cytotoxic T-cell lines : possibility of MTG8 as a tumor antigen recognized by cytotoxic T-cells in AML1/MTG8 fused gene positive acute myelogenous leukemia"Cancer Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maeda M. et al.: "Vaccination of cryoglobulinemia patient with cryoglobulin pulsed monocyto-derived dendritic cells"Leukemia Lymphoma. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Otsuka T, et al.: "Human telomeric protein TRF1 gene expression is downregulated during myeloid differentiation in human hematopoietic cells"Int Hematol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukuyama T, et al.: "Proliferactive involvement of ENX-1, a putative human polycomb group gene, in hematopoietic cells"Brit J Hematol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uchida N, et al.: "Correlation of telomerase activity with development and progression of adult T-cell leukemia"Leuk Res. 23(3). 311-316 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uchida N, et al.: "Differentiatial gene expression of human telomerase-associated protein hTERT and TEP1 in human hematopoietic"Leuk Res. 23(12). 1127-1132 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maeda M,et al.: "Introduction of the MTG8 specific cytotoxic-cell lines : possibility of MTG8 as a tumor antigen recognized by cytotoxic T -cells in AML1/MTG8 fused gene positive acute myelogenous leukemia"Cancer Res:. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Maeda M,et al.: "Vaccination of cryoglobulinemia patient with cryoglobulin pulsed monocyte-derived dendritic cells"Leukemia Lymphoma :. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Otsuka T,et al.: "Human telomeric protein TRF1 gene expression is downregulated during myeloid differentiation in human hematopoietic cells"Int J Hematol :. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukuyama T,et al.: "Proliferative involvement of ENX-1,a putative human polycomb group gene, in haematopoietic cells"Brit J Haematol :. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Uchida N,et al.: "Correlation of telomerase activity with development and progression of adult T-cell leukemia"Leuk Res. 23. 311-316 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uchida N,et al.: "Differential gene expression of human telomerase-associated protein hTERT and TEP1 in human hematopoietic cells"Leuk Res. 23. 1127-1132 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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