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Analysis of expression of tumor-associated antigen, 90 K/Mac-2 binding protein (M2BP) in lung cancer and development of cancer immunotherapy targeting M2BP

Research Project

Project/Area Number 14571262
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionShiga University of Medical Science

Principal Investigator

FUJINO Shozo  Shiga University of Medical Science, Department of Surgery, Associate Professor, 医学部, 助教授 (10209075)

Co-Investigator(Kenkyū-buntansha) KONTANI Keiichi  Shiga University of Medical Science, Department of Surgery, Associate Professor, 医学部, 助手 (90314153)
TEZUKA Noriaki  Shiga University of Medical Science, Department of Surgery, Associate Professor, 医学部, 助手 (40303771)
SAWAI Satoru  Shiga University of Medical Science, Department of Surgery, Associate Professor, 医学部, 助手 (60335172)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordstumor antigen / immunotherapy / Mac-2 binding protein / lung cancer / 90K / 腫瘍関連抗原 / 癌免疫治療 / 90K抗原 / 免疫原性 / 癌免疫療法
Research Abstract

We analyzed the expression of M2BP in lung cancer cells and its immunogenicity as a tumor antigen. Seven of the 8 (87.5%) cultured lung cancer cell lines and 17 of the 28 (60.7%) tumor tissues from patients with primary lung cancer were shown to express high levels of M2BP mRNA. The serum levels of antibodies to M2BP were elevated in 30.4% of the patients. Interestingly, M2BP-specific IgG was observed in all of the patients with anti-M2BP antibodies. Therefore, M2BP is highly expressed in lung cancer and that M2BP-specific immunity was observed in many of patients with lung cancer. These findings suggested the possibility of M2BP to use as a target antigen in cancer immunotherapy. CTLs were generated from peripheral blood lymphocytes of two HLA-A2-positive healthy donors by multiple stimulations in vitro with M2BP-derived peptides showing high affinity to HLA-A2. The CTLs induced using M2BP216-224 (RIDITLSSV) produced interferon-gammain response to HLA-A2-positive T2 cells pulsed with this peptide. Also, the CTLs exhibited specific lytic activity against not only peptide-pulsed T2 cells but also MDA-MB-231 cells expressing both M2BP and HlA-A2. The cytolytic activities were blocked by adding antibodies against HLA class I or CD8 but not by antibodies against HLA class II or CD4. These data suggested that M2BP216-224 is naturally processed from the native M2BP molecule in cancer cells and recognized by M2BP-specific CTLs in an HLA-A2 restriction. We first identified the CTL epitope derived from M2BP and it is expected to be useful as a target antigenic epitope in clinical immunotherapy of lung cancer.

Report

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

    (4 results)

All Other

All Publications (4 results)

  • [Publications] 紺谷桂一: "癌抗原90k/Mac-2 Binding Protein特異的HLA-A24拘束性細胞障害Tリンパ球の誘導とCTLエピトープの同定."乳癌基礎研究会雑誌. 12. 11-15 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ozaki, Y., et al.: "Expression and Immunogenicity of a Tumor-associated Antigen, 90K/Mac-2 Binding Protein, in Lung Cancer"Cancer. 95. 1954-1962 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Ozaki, K.Kontani, J.Hanaoka, T.Chano, K.Teramoto, N.Tezuka, S.Sawai, S.Fujino, T.Yoshiki, H.Okabe, I.Okubo: "Expression and immunogenicity of tumor-associated antigen, 90K/Mac-2 binding protein, in lung carcinoma. The possibility of its clinical use as a tumor marker and a target antigen in cancer immunotherapy"Cancer. 95. 1954-1962 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 紺谷桂一、寺本晃治、尾崎良智、手塚則明、澤井聡、阿部元、花澤一芳、藤野昇三: "癌抗原 90K/Mac-2 Binding Protein 特異的 HLA-A24 拘束性細胞傷害性Tリンパ球の誘導とCTLエピトープの同定"乳癌基礎研究. 12. 11-15 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary

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

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