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Analysis of human tumor immunity using a new model system with endometrial cancer transplanted SCID mice for clinical application

Research Project

Project/Area Number 16591686
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKeio University

Principal Investigator

TSUKAMOTO Makoto  Keio University, School of medicine, Instructor, 医学部, 助手 (50365441)

Co-Investigator(Kenkyū-buntansha) KAWAKAMI Yutaka  Keio University, School of medicine, Professor, 医学部, 教授 (50161287)
AOKI Daisuke  Keio University, School of medicine, Professor, 医学部, 教授 (30167788)
野澤 志朗  慶應義塾大学, 医学部, 教授 (90051557)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsendometrial cancer / MSI / tumor antigen / SCID mouse / Immunodeficiency / 免疫抑制 / T細胞 / 制御性T細胞
Research Abstract

We have developed the new mouse model system in which we are able to observe tumor invasion T cells in the tumor and the spleen as well as a tumor specific human IgG antibody upon transplantation of human tumor tissue into the immune deficiency mouse. In this study, we analyzed the immune responses to the mutated proteins by the microsatellite stability (MSI) which was particularly high in endometrial cancer. The immune response the PTEN frameshift mutation, often observed in MSI-positive endometrial cancers, and the identification of endometrial cancer antigens by SEREX using sera from MSI-positive patients and from MSI-positive tissue transplanted immune deficiency mice were studied. To detect IgG antibody to the frameshift mutated PTEN which was frequently found in endometrial cancer, the full length protein and the frameshift mutated proteins EX7(A4) and EX8(A5) for PTEN were constructed. The antibody for the frameshift mutated protein (EX8) by MSI was detected in a endometrial cancer patient with the EX8 mutation. Cancer-testis antigen SCP-1 and KIAA0445 were identified by SEREX with 3 sera samples from MSI-positive endometrial cancer patients. We performed 3 SEREX experiments using serum from MSI-positive endometrial cancer transplanted immune deficient mice and isolated 18 genes. With previous models, immune responses against 5 of the isolated genes were not detected in patients' sera, so the new model, in which we used sera with the tumor transplanted immune deficiency mice, was effective for the identification of tumor antigens. In 14 of the 18 identified genes, other potential frameshift mutations in the proteins may lead to further targets for immune therapy in future.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (4 results)

All 2005 2004 Other

All Journal Article (4 results)

  • [Journal Article] Frequent immune responses to a cancer/testis antigen,CAGE,in patients with microsatellite instability positive endometrial cancer.2005

    • Author(s)
      Iwata T, Kawakami Y, et al.
    • Journal Title

      Clinical Cancer Res 11・10

      Pages: 3949-3957

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Frequent immune responses to a cancer/testis antigen, CAGE, in patients with microsatellite instability positive endometrial cancer.2005

    • Author(s)
      Iwata T, Kawakami Y, et al.
    • Journal Title

      Clinical Cancer Res 11(10)

      Pages: 3949-3957

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of human tumor antigens and its implication for diagnosis2004

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

      Cancer Sci 95(10)

      Pages: 784-791

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Frequent immune responses to a cancer/testis antigen CAGE in patients

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

      Clin Cancer Res in press

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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