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Expression of MAGE tumor rejection antigen on lung cancer and application for cancer vaccine

Research Project

Project/Area Number 07671491
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKurume University

Principal Investigator

SHICHIJO Shigeki  Kurume Univ. Sch. Med., Dep. Immunol., Associate Prof., 医学部, 助教授 (30080592)

Co-Investigator(Kenkyū-buntansha) ITOH Kyogo  Kurume Univ. Sch. Med., Dep. Immunol., Prof., 医学部, 教授 (50125499)
HAYASHI Akihiro  Kurume Univ. Sch. Med., The First Dep. Surg., Lecturer, 医学部, 講師 (70180958)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsMAGE gene / Lung Cancer / CTLs / tumor rejection antigen / cancer vaccine / MAGE癌退縮抗原遺伝子 / 癌ワクチン / 血清 / 抗体 / ELISA
Research Abstract

(1) Peripheral blood mononuclear cells (PBMC) from lung cancer patients had been stimulared with GST-MAGE-1 or-4 fusion protein. However, we could not induct specific CTL against MAGE antigens. In the other hand, it had been possible to induce specific CTLs against MART-1 peptide restricted in HLA-A2 by the stimulation with this peptide in vitro (Sugita et al., Int. Immunol., 8 (5), 1996). (2) The MAGE genes are frequently expressed in many different cancers, but are not expressed in normal cells or normal tissues other than testis and placenta. Biological roles of proteins of MAGE family remained to be investigated. The expression of MAGE-1 or MAGE-4 protein in the testicular cells was studied immunohistochemically with the antibodies to the recombinant MAGE-1 or MAGE-4 protein. Both proteins were identified in the nucleus and cytoplasm of spermatogonia and in primary spermatocytes but not in spermatids or Sertoli's cells. Therefore, MAGE proteins are normal tissue antigens compartmen … More talized in particular testicular cells playing an important role in the early phase of the spermatogenesis (Takahashi et al, Cancer Res., 55,1995). (3) An enzyme-linked immunosorbent assay (ELISA) was established for measuring cellular MAGE-4 protein expressed on human tumor cells using a monoclonal antibody and polyclonal Ab to recombinant MAGE-4b protein (Shichijo et al., J Immunol. Method, 186,1995). (4) We investigated the level of MAGE-4 protein in sera of patients with primary lung cancer to understand the biological roles of the MAGE proteins. MAGE-4 protein was detected as a non-degraded from in both the supernatant of a MAGE-4^+ tumor cell line and in a patient's serum. Surum level of the MAGE-4 protein in lung cancer patients (n=100, mean=1.17ng/ml) was significantly higher than that in either patients with benign pulmonary diseases (n=80,033ng/ml) or healthy donors (n=68,032ng/ml). It was higher than the cutoff level (1.15ng/ml) in 34 of 100 cancer patients, but not in anyone in the other groups (Shichijo et al., JJCR,in press, 1997). (5) HLA class lrestriction and tumor specificity of cytotoxicity in the IL-2-activated tumor-infiltrating lymphocytes from 16 patients with non-small cell lung cancer were investigated. Six HLA class l-restricted and tumor-specific CTL lines were established : (i) HLA A2-restricted and adenocarcinoma-specific CTLs in three patients with adenocarcinoma, (ii) HLA-A3101-and A3302-restricted and adenocarcinoma-specific CTLs in an HLA-A3101/3302+patients with adenocarcinoma, and (iii) HLA-A3302-restricted CTLs and (iv) HLA-A2402-restricted CTLs recognizing tumors with different types of histology in an HLA-A3302+patients with adenocarcinoma and HLA-A2402 patients with squamous cell carcinoma, respectively (Seki et al., Cell. Immunol., 175,1997). These results showed evidence of the existence of HLA class l-restricted and tumor-specific CTLs recognizing peptide antigens on HLA-A alleles of adenocarcinoma or SCC in tumor sites of a Less

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Shichijo S,: "Induction of MAGE genes in lymphold cells by the demethylating agent 5′-Aza-2-deoxycyildine." Jpn. J. Cancer Res.,. 87. 751-756 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sugita S,: "Melanocyle lysis by cytotoxic T lymphocyte recognlzing the MART-1 melanoma antlgen in IILA-A2 patlents with Vogi-Koyanagi-IIarada disease." Int. Immunol.8(5). 799-803 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toh U: "A monoclonal antibody KIS-1 recognlzing a new membrane antigen on squamous cell carclnoma." Int J Cancer,. 66. 600-606 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwamoto O: "Detection of MAGE-4 prptein in serum of patlents with head and neck squamous cell carchinoma." Int J Cancer. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shichijo S,: "Detection of MAGE-4 protein in sera of lung cancer patlents." Jpn. J. Cancer Res. 88(4). in press (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Seki N: "HLA-A locus-restrlcted and tumor-specific CTLs in lumor-Inflltrating lymphocyles of patlents with non-small cell lung cancer." Cellular Immunol.175(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itoho K: "Melanogenesis and Malignant Melanoma : Biochemistry,Cell Biology,Molecular Biology,Pathophysiology,Diagnosis and Treatment." eds : Horl Y,Hearing VJ and Nakayama J.,ELSEVIER,Amsterdam,The Netherlands,312 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shichijo S,Yamada A,Sagawa K,Iwamoto O,Sakata M,Nagai K,Itoh K: "Induction of MAGE genes in lymphoid cells by the demethylating agent 5'-Aza-2-deoxycytidine" Jpn. J.Cancer Res.87. 751-756 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sugita S,Sagawa K,Mochizuki M,Shichujo S,and Itoh K: "Melanocyte lysis by cytotoxic T lymphocyte recognizing the MART-1 melanoma antigen in HLA-A2 patients with Vogt-Koyanagi-Harada disease." Int. Immunol. 8 (5). 799-803 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toh U,Yamana H,Fujita H,Toh Y,Fujii T,Kubo K,Yamada A,Shichijo S,and Itoh K: "A monoclonal antibody KIS-1 recognizing a new membrane antigen on squamous cell carcinoma." Int J Cancer. 66. 600-606 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itoh K,Hayashi A,Nakao M,Hoshino T,Seki N,and Shichijo S: "Human tumor rejection antigens MAGE." J.Biochem. 119. 385-390 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwamoto O,Nagao Y,Shichijo S,Eura M,Kameyama T,and Itoh K: "Detection of MAGE-4 prptein in serum of patients with head and neck squamous cell carchinoma." Int J Cancer. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shichijo S,Hoshino T,Koufuji K,Hayashi A,Kawamoto M,Kikuchi M,Higuchi T,Ichiki M,Oizumi K,and Itoh K: "Detection of MAGE-4 protein in sera of lung cancer patients." Jpn. J.Cancer Res.88 (4) (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Seki N,Hoshino T,Kikuchi M,Hayashi A,and Itoh K: "HLA-A locus-restricted and tumor-specific CTLs in tumor-infiltrating lymphocytes of patients with non-small cell lung cancer." Cellular Immunol. 175(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itoh K.Hayashi A.Nakao M,Imai Y,Yamada A,Nishida T,Shichijo S: Development of cancer vaccine by tumor rejection antigens.in International Reviews of Immunology, eds : K.Kumagai and S.(in press) Kasakura, Springer-Verlag, New York, (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itoh K,Imai Y,Kuramoto T,Yamad A,Yamana H and Shichijo S: Expression of MAGE-1 and-4 proteinsin normal tissues and various cancers.in Melanogenesis and Malignant Melanoma : Biochemistry, Cell Biology, Molecular Biology, Pathophysiology, Diagnosis and Treatment. eds : Hori Y,Hearing V J and Nakayama J., ELSEVIER,Amsterdam, The Netherlands, 87-96 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shichijo S,: "Induction of MAGE genes in lymphoid cells by the demethylating agent5′-Aza-2-deoxycytidine." Jpn. J. Cancer Res.,. 87. 751-756 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sugita S,: "Melanocyte lysis by cytotoxic T lymphocyle recognizing the MART-1 melanoma antigen in HLA-A2 patients with Vogt-Koyanagi-Harada disease." Int. Immunol.8(5). 799-803 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Toh U: "A monoclonal antibody KIS-1 recognizing a new membrane antigen on squamous cell carcinoma." Int J Cancer,. 66. 600-606 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iwamoto O: "Detection of MAGE-4 prptein in serum of patients with head and neck squamous cell carchinoma." Int J Cancer. in press. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shichijo S: "detection of MAGE-4 protein in sera of lung cancer patients." Jpn. J. Cancer Res. 88(4)in press. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Seki N: "HLA-A locus-restricted and fumor-specific CTLs in tumor-infiltrating lymphocyles of patients with non-small cell lung cancer." Cellular Immunol.175(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Itho K: "eds : Hori Y, Hearing VJ and Nakayama J., ELSEVIER, Amsterdam, The Netherlands" Melanogenesis and Malignant Melanoma : Blochemistry, Cell Biology, Molecular Biology, Pathophysiology, diagnosis and Treatment.1996.

    • Related Report
      1996 Annual Research Report
  • [Publications] Shichijo S.: "Detection MAGE-4 protein in lung cancers." International Journal of Cancer.64,. 158-165 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shigeki S.: "Establishment of an enzyme-linked immunosorbent assay (ELISA) for measuring" Journal of Immunological Methods,. 186. 137-149 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takahashi K,: "Identification of MAGE-1 and -4 proteins in spermatogonia and primary spermatocytes of testis." Cancer Research,. 55,. 3478-3482 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shichijo S.: "Expression of MAGE gene family on human lymphocytic leukemia." Cancer Immunology Immunotherapy,. 41. 95-103 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamada A,: "Expression of MAGE-1, MAGE-2, MAGE-3/-6 genes in ovarian tumors." Int. J. Cancer,. 64,. 388-393 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shichijo S.: "MAGE-1 gene is expressed in T-cell leukemia." Int. J. Cancer,. (in press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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