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Development of cancer immunotherapy using antibody specific for tumor antigens recognized by tumor-infiltration B cells

Research Project

Project/Area Number 17591495
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

TAKENOYAMA Mitsuhiro  University of Occupational and Environmental Health, Japan, School of Medicine, Assistant Professor, 医学部, 講師 (10309966)

Co-Investigator(Kenkyū-buntansha) HANAGIRI Takeshi  University of Occupational and Environmental Health, Japan, School of Medicine, Assistant Professor, 医学部, 講師 (30299614)
SUGAYA Masakazu  University of Occupational and Environmental Health, Japan, School of Medicine, Research Assistant, 医学部, 助手 (40352306)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsSEREX / tumor-infiltrating B cell / tumor antigen / antibody / immunotherapy / lung cancer / マウス
Research Abstract

Recent progress of immunotherapy by antibody have provided us hope of identification of target antigen as a novel immunotherapy. We previously demonstrated that tumor-infiltrating B cells recognized tumor antigens and produced antibodies against them by a using modified SEREX method. In the present study, we have identified tumor-associated antigens in two lung cancer patients and analyzed the usefulness of antigens for tumor marker and immunotherapy. In patient 1 (G603), one of identified antigens was revealed to be MAGE-B2. In the immuno-monitoring of the patient's sera, high antibody titer against MAGE-B2 was observed before operation and the titer decreased after resection of the primary tumor. It was elevated again at the time of adrenal metastasis, but then decreased after resection, indicating that anti-MAGE-B2 antibody could be used as tumor markers for the patient. In patient2, 22 distinct antigens were isolated. Of these antigens, Protein X was highly expressed in 5 out of 9 lung cancer cell lines by RT-PCR. Moreover, Protein X was overexpressed in 9 out of 15 lung cancer tissues compared with corresponding normal lung tissues. Polyclonal antibody against Protein X was generated and was analyzed for localization of antigens and for anti-tumor activity. Flow cytometory showed that Protein X expressed in the cell surface of tumor cells with high expression of this antigen. Immunohistochemical analysis revealed that Protein X was expressed in cell membrane of tumor cells in 7 out of 28 tumor tissues. Tumor implanted in SCID mouse regressed by the inoculation of anti-Protein X antibody. In vitro analysis, anti-tumor acticity was mediated by CDC mechanism. These result indicated that these antigens recognized by TIB could be usefull for clinical diagnosis as a tumor marker and for clinical application of antibody-mediated immunotherapy.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (21 results)

All 2007 2006 2005

All Journal Article (20 results) Book (1 results)

  • [Journal Article] Identification of HLA-A24 restricted shared antigen recognized by autologous cytotoxic T lymphocytes from a patient with large cell carcinoma of the lung.2007

    • Author(s)
      Sugaya, M
    • Journal Title

      Int J Cancer 120(5)

      Pages: 1055-1062

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Lack of tumor recognition by cytolytic T lymphocyte clones recognizing peptide 195-203 encoded by gene MAGE-A3 and presented by HLA-A24 molecules.2007

    • Author(s)
      So, T
    • Journal Title

      Cancer Immunol Immunother 56(2)

      Pages: 259-269

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of HLA-A24 restricted shared antigen recognized by autologous cytotoxic T lymphocytes from a patient with large cell carcinoma of the lung.2007

    • Author(s)
      Sugaya M
    • Journal Title

      International Journal of Cancer 120

      Pages: 1055-62

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A point mutation in the NFYC gene generates an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human squamous cell lung carcinoma.2006

    • Author(s)
      Takenoyama, M
    • Journal Title

      Int J Cancer 118(8)

      Pages: 1992-1997

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of a new cancer/germline gene, KK-LC-1, encoding an antigen recognized by autologous CTL induced on human lung adenocarcinoma.2006

    • Author(s)
      Fukuyama, T
    • Journal Title

      Cancer Res 66(9)

      Pages: 4922-4928

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of IgG produced by tumor-infiltrating B lymphocytes on lung tumor growth.2006

    • Author(s)
      Mizukami, M
    • Journal Title

      Anticancer Research 26(3)

      Pages: 1827-1831

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Antigens recognized by IgG derived from tumor-infiltrating B lymphocytes in human lung cancer.2006

    • Author(s)
      Yasuda, M
    • Journal Title

      Anticancer Res 25(5)

      Pages: 3607-3612

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Antigens recognized by IgG derived from tumor-infiltrating B lymphocytes in human lung cancer2006

    • Author(s)
      Yasuda M
    • Journal Title

      Anticancer Research 26

      Pages: 3607-11

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of IgG produced by tumor-infiltrating B lymphocytes on lung tumor growth.2006

    • Author(s)
      Mizukami M
    • Journal Title

      Anticancer Research 26

      Pages: 1827-31

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of a new cancer/germline gene, KK-LC-1,encoding an antigen recognized by autologous CTL induced on human lung adenocarcinoma.2006

    • Author(s)
      Fukuyama T
    • Journal Title

      Cancer Research 66

      Pages: 4922-28

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A point mutation in the NFYC gene generates an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human squamous cell lung carcinoma.2006

    • Author(s)
      Takenoyama M
    • Journal Title

      International Journal of Cancer 118

      Pages: 1992-97

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A point mutation in the NFYC gene generated as an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human squamous cell lung carcinoma2006

    • Author(s)
      Takenoyama M
    • Journal Title

      Int J Cancer 118(8)

      Pages: 1992-1997

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tumor specific expression of survivin-2B in lung cancer as a novel target of immunotherapy.2005

    • Author(s)
      Ichiki, Y
    • Journal Title

      Lung Cancer 48

      Pages: 281-289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of the HLA-Cw*0702-restricted tumor-associated antigen recognized by a CTL clone from a lung cancer patient.2005

    • Author(s)
      Nagata, Y
    • Journal Title

      Clin Cancer Res 11(14)

      Pages: 5265-5272

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Haplotype loss of HLA class I antigen as an escape mechanism from immune attack in lung cancer.2005

    • Author(s)
      So, T
    • Journal Title

      Cancer Res 65(13)

      Pages: 5945-5952

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of tumor associated antigens recognized by IgG from tumor-infiltrating B cells of lung cancer : correlation between Ab titer of the patient's sera and the clinical course.2005

    • Author(s)
      Mizukami, M
    • Journal Title

      Cancer Sci 96(12)

      Pages: 882-888

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tumor specific expression of survivine-2B in lung cancer as a novel target of Immunotherapy2005

    • Author(s)
      Ichiki Y
    • Journal Title

      Lung Cancer 48(2)

      Pages: 281-289

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Haplotype loss of HLA class I antigen as an escape mechanism from immune attack in lung cancer2005

    • Author(s)
      So T
    • Journal Title

      Cancer Res 65(13)

      Pages: 5945-5952

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification of the HLA-Cw*0702-restricted tumor-associated antigen recognized by a CTL clone from a lung cancer patient2005

    • Author(s)
      Nagata Y
    • Journal Title

      Clin Cancer Res 11(4)

      Pages: 5265-5272

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification of tumor associated antigens recognized by IgG from tumor-infiltrating B cells of lung cancer : correlation between Ab titer of the patient's sera and the clinical course2005

    • Author(s)
      Mizukami M
    • Journal Title

      Cancer Sci 96(12)

      Pages: 882-888

    • Related Report
      2005 Annual Research Report
  • [Book] 肺癌の臨床-肺癌の免疫療法2005

    • Author(s)
      花桐武志, 安元公正
    • Total Pages
      297
    • Publisher
      篠原出版社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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