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2004 Fiscal Year Final Research Report Summary

Novel immunogene therapy for hematopoietic malignancies

Research Project

Project/Area Number 15390301
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionEhime University

Principal Investigator

YASUKAWA Masaki  Ehime University, School of Medicine, Associate Professor, 医学部, 助教授 (60127917)

Co-Investigator(Kenkyū-buntansha) YAKUSHIJIN Yoshihiro  Ehime University, School of Medicine, Instructor, 医学部, 助手 (30294797)
UCHIDA Hiroyuki  Ehime University, University Hospital, Instructor, 医学部附属病院, 助手 (80359926)
Project Period (FY) 2003 – 2004
Keywordshematopoietic malignancies / cytotoxic T lymphocyte / WT1 / cancer vaccine / immunodefcient mice / T-cell receptor
Research Abstract

We performed studies on immunogene therapy for hematopoietic malignanicies. The data obtained from the series of study are as follows. 1) Myeloma cells are sensitive to perforin-dependent cytotoxicity mediated by WT1-specifici cytotoxic T lymphocytes (CTLs). 2)There is a difference in the control of perforin expression between CD4^+ and CD8^+ CTLs ; that is, perforin is expressed constitutively in memory CD8^+ CTLs, but is dependent on cell activation in memory CD4^+ CTLs. 3)T-cell receptor (TCR) α and β genes obtained from an HLA-A24-restricted, WT1 peptide-specific CTL clone were lentivirally transduced to polyclonally-activated T lymphocytes. TCR gene-transduced CD4+ and CD8+ T lymphocytes showed HLA-A24-restricted and WT1-specific reactivity against leukemia cells. 4)The WT1-derived epitope recognized by HLA-DP5-restricted CD4+ T-cell clone was identified. WT1-specific CD4+ T-cell clone exerted the perforin-dependent cytotoxicity against leukemia cells. 5)Phase I clinical study of cancer peptide vaccine using WT1-derived and hTERT-derived peptides has been continued. 6) Human immune system was constructed in the novel immundeficient mice by transplantation of human hematopoietic stem cells.

  • Research Products

    (12 results)

All 2005 2004 2003 Other

All Journal Article (12 results)

  • [Journal Article] Generation of human tumor-specific, HLA class I-restricted Th1 and Tc1 cells by cell engineering with tumor peptide-specific T cell receptor genes2005

    • Author(s)
      Tsuji T, et al.
    • Journal Title

      Blood (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genetic subtypes of familial hemophagocytic lymphohistiocytosis, correlations with clinical features and cytotoxic T lymphocyte/natural killer cell functions2005

    • Author(s)
      Ishii e, et al.
    • Journal Title

      Blood (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Human cord blood-and bone marrow-derived CD34^+ cells regenerate gastrointestinal epithelial cells2004

    • Author(s)
      Ishikawa F, et al.
    • Journal Title

      FASEB J. 18

      Pages: 1958-1960

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of novel MUNC13-4 mutations in familial hemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes2004

    • Author(s)
      Yamamoto K, et al.
    • Journal Title

      J.Med.Genet. 41

      Pages: 763-767

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Myeloma cells are highly sensitive to granule exocytosis pathway mediated by WT1-specific cytotoxic T lymphocytes2004

    • Author(s)
      Azuma T, et al.
    • Journal Title

      Clin,.Cancer Res. 10

      Pages: 7402-7412

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Human cord blood- and bone marrow-derived CD34^+ cells regenerate gastrointestinal epithelial cells.2004

    • Author(s)
      Ishikawa, F., Yasukawa, M., Yoshida, S., Shimoda, K., Shimoda, S., Nakamura, K., Nagatoshi, Y., Kanemaru, T., Kawano, N., Nagafuji, K., Miyamoto, T., Fukuda, T., Okamura, J., Shultz, L.D., Harada, M.
    • Journal Title

      FASEB J. 18

      Pages: 1958-1960

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of novel MUNC13-4 mutations in familial hemophagocytic lymphohistiocytosis and functional analysis of MUNC 13-4-deficient cytotoxic T lymphocytes.2004

    • Author(s)
      Yamamoto, K., Ishii, E., Sako, M., Ohga, S., Furuno, K., Suzuki, N., Ueda, I., Imayoshi, M., Yamamoto, S., Morimoto, A., Takada, H., Hara, T., Imashuku, S., Sasazuki, T., Yasukawa, M.
    • Journal Title

      J.Med.Genet. 41

      Pages: 763-767

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Myeloma cells are highly sensitive to granule exocytosis pathway mediated by WT1-specific cytotoxic T lymphocytes.2004

    • Author(s)
      Azuma, T., Otsuki, T., Kuzushima, K., Froelich, C., Fujita, S., Yasukawa, M.
    • Journal Title

      Clin.Cancer Res. 10

      Pages: 7402-7412

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Essential roles of perforin in antigen-specific cytotoxicity mediated by human CD4^+ T lymphocytes : analysis using the combination of hereditary perforin-deficient effector cells and Fas-deficient target cells2003

    • Author(s)
      Yanai F, et al.
    • Journal Title

      J.Immunol. 170

      Pages: 2205-2213

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Essential roles of perforin in antigen-specific cytotoxicity mediated by human CD4^+ T lymphocytes : analysis using the combination of hereditary perforin-deficient effector cells and Fas-deficient target cells.2003

    • Author(s)
      Yanai, F., Ishii, E., Kojima, K., Hasegawa, A., Azuma, T., Hirose, S., Suga, N., Mitsudome, A., Zaitsu, M., Ishida, Y., Shirakata, Y., Sayama, K., Hashimoto, K., Yasukawa, M.
    • Journal Title

      J.Immunol. 170

      Pages: 2205-2213

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Generation of human tumor-specific, HLA class I-restricted Th1 and Tc1 cells by cell engineering with tumor peptide-specific T cell receptor genes.

    • Author(s)
      Tsuji, T., Yasukawa, M., Matsuzaki, J., Ohkuri, T., Chamoto, K., Azuma, T., Niiya, H., Miyoshi, H., Takeshima, T., Ikeda, H., Nishimura, T.
    • Journal Title

      Blood (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genetic subtypes of familial hemophagocytic lymphohistiocytosis : correlations with clinical features and cytotoxic T lymphocyte/natural killer cell functions.

    • Author(s)
      Ishii, E., Ueda, I., Shirakawa, R., Yamamoto, K., Horiuchi, H., Ohga, S., Furuno, K., Morimoto, A., Imayoshi, M., Ogata, Y., Sako, M., Koike, K., Sakata, A., Takada, H., Hara, T., Imashuku, S., Sasazuki T., Yasukawa, M.
    • Journal Title

      Blood (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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