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WT1 protein-targeted immunotherapy for leulemia

Research Project

Project/Area Number 15109007
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionOsaka University

Principal Investigator

SUGIYAMA Haruo  Osaka University, Graduate School of Medicine, Dept of Functional Diagnostic Science, Professor (70162906)

Co-Investigator(Kenkyū-buntansha) OKA Yoshihiro  Osaka University, Dept of Molecular Medicine, Associate Professor (20273691)
OJI Yusuke  Osaka University, Dept of Molecular Medicine, Associate Professor (20294100)
小川 啓恭  大阪大学, 医学系研究科, 助教授 (80194447)
Project Period (FY) 2003 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥118,950,000 (Direct Cost: ¥91,500,000、Indirect Cost: ¥27,450,000)
Fiscal Year 2007: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2006: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2005: ¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000)
Fiscal Year 2004: ¥35,100,000 (Direct Cost: ¥27,000,000、Indirect Cost: ¥8,100,000)
Fiscal Year 2003: ¥37,050,000 (Direct Cost: ¥28,500,000、Indirect Cost: ¥8,550,000)
KeywordsWT1 / leukemia / myelochisplastic syndrome / immunotherany / Wilm's tumor gene / Wilms' tumor gene
Research Abstract

A phase I clinical study to assess the safety of WT1 peptide vaccination was started in 2001. Natural (CMTWNQMNL) or modified (CYTWNQMNL) WT1 peptide emulsified with montanide adjuvant was intradermally injected with dose escalation of 0.3 mg/body, 1.0mg/body and 3.0mg/body. This WT1 vaccination was performed three times at 2-weeks intervals. Eight of 12 AML patients who were WT1-vaccinated had minimal residual disease of leukemia. Four of these eight AML patients had clinical effect and three of the four are being WT1-vaccinated for more than 5 years until now. These three patients don't have significant adverse effect and enjoy long-term continuous complete remission. On the other hand, a new phase I clinical study, in which a very low dose of WT1 peptide, such as 5 μg/body ,15 μg/body, or 50 μg/body, is vaccinated to avoid rapid reduction of leukocytes, have started.

Report

(6 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (26 results)

All 2009 2007 2006 2005 2004 2003 Other

All Journal Article (19 results) (of which Peer Reviewed: 6 results) Presentation (2 results) Remarks (2 results) Publications (3 results)

  • [Journal Article] Clinical and immunologic responses to very low-dose vaccination with WT1 peptide(5 mug/body)in a patient with chronic myelomonocytic leukemia.2007

    • Author(s)
      Kawakami M., et. al.
    • Journal Title

      International Journal of Hematology 85

      Pages: 426-429

    • 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] Clinical and immunologic responses to very low-dose vaccination with WT1 peptide(5 mug/body)in a patient with chronic myelomonocytic leukemia.2007

    • Author(s)
      Kawakami, M, et. al.
    • Journal Title

      Int J Hematol 85

      Pages: 426-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Identification and characterization of a WT1 (Wilms' tumor gene) protein-derived HLA-DRB1*0405-restricted 16-mer helper peptide that promotes the induction and activation of WT1-specific cytotoxic T lymphocytes.2007

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

      J Immnunother. 30

      Pages: 282-293

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and immunologic responses to very low-dose vaccination with WT1 peptide (5 mug/body) in a patient with chronic myelomonocytic leukemia.2007

    • Author(s)
      Kawakami M, et. al.
    • Journal Title

      Int J Hematol. 85

      Pages: 426-429

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wilms' tumor gene WT1 peptide-based immunotherapy induced minimal response in a patient with advanced, therapy-resistant multiple myeloma.2007

    • Author(s)
      Tsuboi A, et. al.
    • Journal Title

      Int J Hematol. 86

      Pages: 414-417

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Phase I/II Trial of a WT1 (Wilms' Tumor Gene) Peptide Vaccine in Patients with Solid Malignancy : Safety Assessment Based on the Phase I Data.2006

    • Author(s)
      Morita, S., et al.
    • Journal Title

      J. J. Clin. Oncol. 36

      Pages: 231-236

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Prognostic significance of Wilms tumor gene (WT1) mRNA expression in soft tissue sarcoma.2006

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

      Cancer 106

      Pages: 2233-2240

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Immunohistochemical detection of WT1 protein in a variety of cancer cells.2006

    • Author(s)
      Nakatsuka, S., et al.
    • Journal Title

      Mod. Pathol. 19

      Pages: 804-814

    • Related Report
      2006 Annual Research Report
  • [Journal Article] WT1(235), a ninemer peptide derived from Wilms' tumor gene product, is a candidate peptide for the vaccination of HLA-A^*0201-positive patients with hematopoietic malignancies.2005

    • Author(s)
      Li, Z., et al.
    • Journal Title

      Int J Hematol. 82

      Pages: 458-459

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Th1-biased humoral immune responses against Wilms tumor gene WT1 product in the patients with hematopoietic malignancies.2005

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

      Leukemia 19

      Pages: 268-274

    • Related Report
      2005 Annual Research Report
  • [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.2005

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

      Blood 106

      Pages: 470-476

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Induction of WT1(Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression.2004

    • Author(s)
      Oka Y., et. al.
    • Journal Title

      Proc Natl Acad Sci USA 101

      Pages: 13885-13890

    • 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 WT1(Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression.2004

    • Author(s)
      Oka, Y, et. al.
    • Journal Title

      Proc Natl Acad. Sci USA 101

      Pages: 13885-13890

    • 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 WT1 (Wilms' tumor gene)-specific cytotoxic Tlymphocytes by WT1 peptide vaccine and the resultant cancer regression.2004

    • Author(s)
      Oka, Y.et al.
    • Journal Title

      Proceedings of National Academy of Science USA 101・38

      Pages: 13885-13890

    • Related Report
      2004 Annual Research Report
  • [Journal Article] WT1 peptide vaccination combined with BCG-CWS is more efficient for tumor eradication than WT1 peptide vaccination alone.2004

    • Author(s)
      Nakajima, H et al.
    • Journal Title

      Cancer Immunology and Immunotherapy 53・7

      Pages: 617-624

    • Related Report
      2004 Annual Research Report
  • [Journal Article] WT1 peptide-based immunotherapy for patients with overt leukemia from myelodysplastic syndome(MDS)or MDS with myelofibrosis.2003

    • Author(s)
      Oka Y., et al.
    • Journal Title

      International Journal of Hematology 78

      Pages: 56-61

    • 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] WT1 peptide-based immunotherapy for patients with overt leukemia from myelodysplastic syndrome(MDS) or MDS with myelofibrosis.2003

    • Author(s)
      Oka, Y, et. al.
    • Journal Title

      International Journal of Hematology 78

      Pages: 56-61

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Identification and characterization of a WT1 (Wilms' tumor gene) protein-derived HLA-DRB1^*0405-restricted 16-mer helper peptide that Promotes the induction and activation of WT1-specific cytotoxic Tlymphocytes.

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

      J Immunother. (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A phase I/II trial of WT 1 (Wilms' tumor gene peptide vaccine in patients with solid malignancy : Safety assessment based on the phase I data.

    • Author(s)
      Morita, S., et al.
    • Journal Title

      Jpn J Clin Oncol (In press)

    • Related Report
      2005 Annual Research Report
  • [Presentation] WT1 peptide vaccination at very low-dose for myelodysplastic syndrome.2009

    • Author(s)
      Kawakami, M, et. al.
    • Organizer
      3rd International Conference on WT1 in Human Malignancies, Berlin
    • Year and Date
      2009-09-19
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] WT1 peptide vaccination at very low-dose for myelodysplastic syndrome.2007

    • Author(s)
      Kawakami M., et. al.
    • Organizer
      3rd International Conference on WT1 in Human Malignallcies
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2007-09-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://sahswww.med.osaka-u.ac.jp/%7Ehmtonc/index.html

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://sahswww.med.osaka-u.ac.jp/%7Ehmtonc/index.html

    • Related Report
      2007 Annual Research Report
  • [Publications] Tsuboi, A. et al.: "WT1 peptide-based immunotherapy for patients with lung cancer"Microbiology and Immunology. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakajima, H. et al.: "WT1 peptide vaccination combined with BCG-CWS is more efficient for tumor eradiation than WT1 peptide vaccination alone"Cancer Immunology and Immunotherapy. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Oka, Y.et al.: "WT1 peptide-based immunotherapy for patients with overt leukemia from myelodysplastic syndome (MDS) or MDS with myelofibrosis"International Journal of Hematology. 78. 56-61 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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