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Immunotherapy of leukemias by targeting hematopoietic lineage-specific minor histocompatibility antigens

Research Project

Project/Area Number 13671092
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionAichi Cancer Center

Principal Investigator

AKATSUKA Yoshiki  Aichi Cancer Center Division of Immunology, Senior Researcher, 腫瘍免疫学部, 主任研究員 (70333391)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Toshitada  Aichi Cancer Center Research Institute, Director, 研究所, 所長 (00124529)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsMinor histocompatibility antigen / Cytotoxic T lymphocyte / Adoptive immunotherapy / Leukemia / 細胞障害性T細胞 / マイナー組織適合性抗原
Research Abstract

Cytotoxic T lymphocytes (CTL) specific for minor histocompatibility antigens (mHAgs) whose tissue expression is limited to hematopoietic cells are useful for immunotherapy of relapsed leukemia following allogeneic hematopoietic cell transplantation (HCT). We have obtained peripheral blood samples from 26 patients receiving HCT during the research period and attempted to generate CTL restricted by HLA-A24, the most common HLA in Japanese. To facilitate the procedure, we devised a novel method to screen for the presence of mHAgs-specific CTL restricted by HLA of interest in CTL lines by using HLA transfected B lymphoblastoid cell lines retrovirally and interferon-gamma release-based assays. We successfully generated 4 distinct HLA-A24-restricted CTL clones. By using LCL from members of large CEPH families whose genetic markers had been typed in combination with linkage analysis, gene(s) encoding mHAgs detectable 2 distinct CTL restricted by HLA-A24 and B44 were located at chromosome 15q24.5. Of 39 genes within the region, we determined the gene encoding the mHAgs using various online databases (dbSNP, SAGE, UCSC Human Genome Browser) and softwares (BIMAS). The gene, BCL2A1, possesses three single nucleotide polymorphisms, two of which turned out to encode two mHAgs epitopes detected by the 2 CTL clones used. BCL2A1 is expressed in only hematopoietic cells, thus is thought to be a good candidate for immunotherapy of leukemia. We have successfully induced CTL lines specific for the BCL2A1 mHAg using peptide-pulsed antigen presenting cells. We plan on conducting a phase I clinical study of adoptive immunotherapy for patients with relapsed leukemia following allogeneic HCT using ex vivo expanded CTL clones specific for the BCL2A1 mHAgs.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Yoshiki Akatsuka: "Identification of a Polymorphic Gene, BCL2A1, Encoding Two Novel Hematopoietic Lineage-specific Minor Histocompatibility Antigens"Journal of Experimental Medicine. 197(in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mikinori Miyazaki: "Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells"Clinical Immunology. 107(in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshiki Akatsuka: "Targeted cloning of cytotoxic T cells specific for minor histocompatibility antigens restricted by HLA class I molecules of interest"Transplantation. 74. 1773-1780 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Eisei Kondo: "Efficient generation of antigen-specific cytotoxic T cells using retrovirally transduced CD40-activated B cells"Journal of Immunology. 169. 2164-2171 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshiki Akatsuka: "Efficient cloning and expression of HLA class I cDNA in human B-lymphoblastoid cell lines"Tissue Antigens. 59. 502-511 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 赤塚 美樹: "マイナー組織適合抗原の生物学的意義"最新医学. 56. 186-191 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshiki Akatsuka: "Identification of a Polymorphic Gene, BCL2A1, Encoding Two Novel Hematopoietic Lineage-specific Minor Histocompatibility Antigens"Journal of Experimental Medicine. vol.197(In press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mikinori Miyazaki: "Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells"Clinical Immunology. vol.107(In press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshiki Akatsuka: "Targeted cloning of cytotoxic T cells specific for minor histocompatibility antigens restricted by HLA class I molecules of interest"Transplantation. 74. 1773-1780 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Eisei Kondo: "Efficient generation of antigen-specific cytotoxic T cells using retrovirally transduced CD40-activated B cells"Journal of Immunology. 169. 2164-2171 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshiki Akatsuka: "Efficient cloning and expression of HLA class I cDNA in human B-lymphoblastoid cell lines"Tissue Antigens. 59. 502-511 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshiki Akatsuka: "Minor histocompatibility antigens and their clinical significance"Saishin Igaku. 56. 186-191 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Eisei Kondo: "Efficient generation of antigen-specific cytotoxic T cells using retrovirally transduced CD40-activated B cells"Journal of Immunology. 169. 2164-2171 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshiki Akatsuka: "Targeted cloning of cytotoxic T cells specific for minor histocompatibility antigens restricted by HLA class I molecules of interest"Transplantation. 74. 1773-1780 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mikinori Miyazaki: "Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells"Clinical Immunology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshiki Akatsuka: "Efficient cloning and expression of HLA class I cDNA in human B-lymphoblastoid cell lines"Tissue Antigens. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 赤塚 美樹: "マイナー組織適合抗原の生物学的意義"最新医学. 56. 186-191 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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