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Establishment of tumor specific immunotherapy for lung cancer patients ; Identification of tumor antigens and analysis of immune responses.

Research Project

Project/Area Number 14370420
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

YASUMOTO Kosei  University of Occupational and Environmental Health Japan, School of Medicine, Professor, 医学部, 教授 (30150452)

Co-Investigator(Kenkyū-buntansha) SUGIO Kenji  University of Occupational and Environmental Health, Japan, School of Medicine, Associate Professor, 医学部, 助教授 (70235927)
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 Associate, 医学部, 助手 (40352306)
竹之山 光広  産業医科大学, 医学部, 助手 (10309966)
山下 智弘  産業医科大学, 医学部, 助手 (30341530)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥8,600,000 (Direct Cost: ¥8,600,000)
KeywordsLung cancer / tumor antigen / peptide / CTL / SEREX / immunotherapy / vaccine / antibody
Research Abstract

It is very important to analyze tumor-specific immune responses in cancer patients for development of effective tumor specific immunotherapy. We have established 21 lung cancer cell lines and induced tumor-specific cytotoxic T lymphocytes (CTL) from regional lymph node lymphocytes in lung cancer patients. Several tumor associate antigens recognized by these CTLs were identified by cDNA expression cloning method. CTL Clone 1 and Clone 2 recognized autologous large cell carcinoma (A904L), whereas they did not respond to autologous EBV-B and PHA-blastoid T cells. Clone 1 recognized the tumor antigen restricted by HLA-A24. The antigen coding gene revealed a splicing variant of known gene. On the other hand, Clone 2 recognized the tumor antigen in the context of HLA-Cw7. The antigen coding gene was a function-unknown gene. The tumor specific CTL clone H1 against adenocarcinoma cell line (F1121L) was induced from regional lymph node lymphocytes. This CTL clone lysed autologous tumor cells in … More the context of HLA-B^*1507. The antigen recognized by the CTL was a new cancer/testis antigen. Identification of these lung cancer associated antigen facilitates peptide based specific immunotherapy for lung cancer patients.
In order to investigate the potential role of tumor-infiltrating B cells (TIB) in lung cancer, we demonstrated that humoral immune responses of TIB in lung cancer patients could be detected in SLID mice xenotransplanted model. By serological analysis of recombinant cDNA expression libraries (SERER), 25 distinct antigens reactive with IgG derived from TIB were identified in two lung cancer cell lines. Sequencing analysis showed that the functions of 14 antigens were known, and the function of other 11 genes were unknown. Furthermore, 4 out of the identified genes had extra-cellular region. These findings suggested that TIB-derived IgG played an important role in humoral immune response against lung cancer. The identified cancer related antigens may have a potential target for cancer vaccines and monoclonal antibody-based immunotherapies. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (28 results)

All 2005 2004 2003 2002 Other

All Journal Article (18 results) Publications (10 results)

  • [Journal Article] A different pattern of cytotoxic T lymphocyte recognition against primary and metastatic tumor cells in a patient with nonsmall cell lung carcinoma2005

    • Author(s)
      So T
    • Journal Title

      Cancer 103

      Pages: 200-208

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Tumor specific expression of surviving-2B in lung cancer as a novel target of immunotherapy2005

    • Author(s)
      Ichiki Y
    • Journal Title

      Lung Cancer (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A different pattern of cytotoxic T lymphocyte recognition against primary and metastatic tumor cells in a patient with nonsmall cell lung carcinoma.2005

    • Author(s)
      So T
    • Journal Title

      CANCER 103(1)

      Pages: 200-208

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [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(2)

      Pages: 281-289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tumor specific expression of survivin-2B in lung cancer as a novel target of immunotherapy2005

    • Author(s)
      Ichiki Y
    • Journal Title

      Lung Cancer (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Simultaneously cellular and humoral immune response against mutated p53 in a patient with ling cancer2004

    • Author(s)
      Ichiki Y
    • Journal Title

      J Immunology 172

      Pages: 4844-4850

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Simultaneous cellular and humoral immune response against mutated p53 in a patient with lung cancer.2004

    • Author(s)
      Ichiki Y
    • Journal Title

      The journal of immunology 172

      Pages: 4844-4850

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Simultaneously cellular and humoral immune response against mutated p53 in a patient with lung cancer2004

    • Author(s)
      Ichiki Y
    • Journal Title

      J Immunology 172

      Pages: 4844-4850

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 肺癌浸潤過程における接着分子の関与とその情報伝達による免疫回避機構の解析2003

    • Author(s)
      Yasuda M
    • Journal Title

      Biotherapy 17(2)

      Pages: 113-138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Survival and prognostic factors of surgically resected T4 non-small cell lung cancer.2003

    • Author(s)
      Yasumoto K
    • Journal Title

      Ann Thorac Surg 76(1)

      Pages: 194-202

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 肺癌浸潤過程における接着分子の関与とその情報伝達による免疫回避機構の解析2003

    • Author(s)
      Yasuda M
    • Journal Title

      Biotherapy 17・2

      Pages: 131-138

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Tumor-infiltrating B lymphocytes as a potential source of identifying tumor antigen in human line cancer2002

    • Author(s)
      Yasuda M
    • Journal Title

      Cancer Research 62

      Pages: 1751-1756

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Establishment of fifteen cancer cell lines from patients with lung cancer the potential tools for immunotherapy2002

    • Author(s)
      Sugaya M
    • Journal Title

      Chest 122(1)

      Pages: 282-288

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Establishment of 15 cancer cell lines from patients with lung cancer and the potential tools for immunotherapy.2002

    • Author(s)
      Sugaya M
    • Journal Title

      Chest 122

      Pages: 282-288

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] CD44:functional relevance to inflammation and malignancy.2002

    • Author(s)
      Yasuda M
    • Journal Title

      Histology and Histopathology 17

      Pages: 945-950

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Establishment of an immortalized T-cell line from lung cancer tissue: phenotypic and functional analyses.2002

    • Author(s)
      Imahayashi S
    • Journal Title

      International Journal of Clinical Oncology 7(1)

      Pages: 38-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tumor-infiltrating B lymphocytes as a potential source of identifying tumor antigen in human lung cancer.2002

    • Author(s)
      Yasuda M
    • Journal Title

      Cancer Research 62

      Pages: 1751-1756

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Establishment of Fifteen Cancer Cell Lines from Patients With Lung Cancer and the Potential Tools for Immunotherapy2002

    • Author(s)
      Sugaya M
    • Journal Title

      Chest 122・1

      Pages: 282-288

    • Related Report
      2004 Annual Research Report
  • [Publications] Ichiki Y: "Simultaneous cellular and humoral immune response against mutated p53 in a patient with lung cancer"J Immunology. In press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugio K: "Genetic alteration in carcinoid tumors of the lung."Ann Thorac Cardiovasc Surg.. 9・3. 149-154 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 竹之山光広: "肺癌の免疫療法"Mook肺癌の臨床 Annual Review 2003. 223-227 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 菅谷 将一: "肺癌に対する免疫療法の現況と展望"呼吸器科. 4. 243-248 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugaya M: "Establishment of 15 cancer cell lines from patients with lung cancer and the potential tools for immunotherapy"Chest. 122・1. 282-288 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Imahayashi S: "Establishment of an immortalized t-cell from lung cancer tissue : phenotypic and functional analyses"Int J Clin Oncol. 7・1. 38-44 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasuda M: "Tumor-infiltrating B lymphocytes as a potential source of identifying tumor antigen in human lung cancer"Cancer Res. 62・6. 1751-1756 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasuda M: "CD44 : functional relevance to inflammation and malignancy"Histol Histopathol. 17・3. 945-950 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osaki T: "Prognostic impact of micrometastatic tumor cells in the lymph nodes and bone marrow of patients with completely resected stage I non-small-cell"J Clin Oncol. 20・13. 2930-2936 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Gu CD: "Detection of micrometastatic fumor cells in pNO lymph nodes of patients with completely resected nonsmall cell lung cancer : impact on recurrence and Survival"Ann Surg. 235・1. 133-139 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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