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Development of cancer vaccine with MAGE gene products.

Research Project

Project/Area Number 07457284
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

ITOH Kyogo  Kurume Univ. Sch. Med., Dep. Immunol., Prof., 医学部, 教授 (50125499)

Co-Investigator(Kenkyū-buntansha) NAKAO Masanobu  Kurume Univ. Sch. Med., Dep. Immunol., Res. Associa., 医学部, 助手 (40258447)
YAMANA Hideaki  Kurume Univ. Sch. Med., The First Dep. Surg., Associa. Prof., 医学部, 助教授 (30140669)
SAITSU Hideki  Kurume Univ. Sch. Med., The Second Dep. Surg., Lecturer, 医学部, 講師 (60186921)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1996: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1995: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsMAGE gene / Tumor-rejection antigen / Cancer Vaccine / Lung Cancer / Serum MAGE-4 protein / Cancer of digestive tract / cytotoxic Tlymphocytes / tumor-infiltrating lymphocytes / 癌退縮抗原 / MAGE / HLA-class I拘束性 / ペプチドワクチン
Research Abstract

The MAGE-1, -2, -3, -4, -6, and -12genes are frequently expressed in many different cancers, but are not expressed in normal cells or normal tissues other than testis and placenta. MAGE-1 and -3 peptides are currently used as vaccines for cancer patients, and three of 12 HLA-A1 patients with metastatic melanoma responded to MAGE-3 peptide. Therefore, MAGE protein could be a potential vaccine for HLA-A1 cancer patients. However, CTL were not detected in the peripheral blood of the responding patients, and there was no available monitoring methods to know the efficacy of MAGE vaccine. Further, biological roles of proteins of MAGE family remain to be investigated. We investigated serum level of MAGE-4 protein, one of the family of MAGE proteins, in various cancer patients. MAGE-4 protein was detected as a non-degraded form in both the supernatant of MAGE-4^+ tumor cell line and serum of cancer patients with different types of histology (lung cancer, head and neck cancer, and hepatocellula … More r carcinomas. For example, serum level of the MAGE-4 protein of lung cancer patients (n=100, mean=1.17ng/ml) was significantly (p=0.0013) higher than that of either patients with benign pulmonary diseases (n=80, mean=0.33ng/ml) or HD (n=68, mean=0.32ng/ml) (Shichijo et al., JJCR,in press, 1977). The serum level of MAGE-4 was higher than the cutoff level (1.15ng/ml) in 34 of 100 cancer patients, but no one in the other groups reached the cutoff level. The similar results were obtained in sera of the other cancer patients. In addition, it is of note that surgical removal of tumor mass resulted in decrease of serum level of MAGE-4 protein and recurrence was associated with it's reincrease (Iwamoto et al., Int. J.Cancer, in press, 1997). Furthermore, serum MAGE-4 was significantly higher in patients with both hepatocellular carcinoma and hepatitis C virus positive liver cirrhosis, a high risk group of hepatocellular carcinoma. These information could be important for better understanding of biological roles of MAGE proteins, and measurement of serum levels of MAGE-4 protein could be useful for detection of MAGE-4^+ cancers with different types of histology.
HLA class I-restricted and tumor-specific CTLs have been observed in T cells of peripheral blood mononuclear cells (PBMC) stimulated with autologous tumor cells or IL-2-activated tumor infiltrating lymphocytes (TILs) of patients with melanomas. Genes encoding peptide antigens recognized by CTLs have been cloned from melanomas using these CTLs. However, either the presence of these CTLs or peptide antigens have been rarely reported in either adenocarcinoma of squamous cell carcinoma, two major human cancers needed for development of new treatment modalities. We have investigated HLA-A locus-restriction and tumor-specificity of IL-2 activated TILs from esohageal cancers, gastric cancers, colon cancers and lung cancers. The results showed the presence of HLA class lredtricted and tumor specific CTLs in TILs of esophageal cancers (Toh et al., Cell lmmunol. in press, 1997), gastric cancers (Hoshino et al., Int. J.Cancer in press, 1997), colon cancers (Gouhara et al., JJCR,in press, 1997) and non-small lung cancers (Seki et al., Cell lmmunolo. in press, 1997). These CTLs could be a tool for identification of genes encoding tumor-rejection antigens for development of cancer vaccines. Less

Report

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

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Takahashi,K.,Itoh K. et al.: "Identification of MAGE-1 and-4 proteins in spermatogonia and primary spermatocytes of testis." Cancer Res.55. 3478-3482 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakao,M.,Itoh,K. et al.: "HLA A2601-restricted cytotoxic T lymphocytes recognizing a peptide antigen expressed on squamous cell carcinoma" Cancer Res.55. 4248-4252 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shichijo.S.,Itoh,K. et al.: "Induction of MAGE genes in lymphoid cells by the demethylating agent 5′-Aza-2′-deoxycytidine" JJCR. 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] Shichijo.S.,Itoh,K. et al.: "MAGE-1 gene is expressed in T cell leukemia." (Letter),Int. J. Cancer,. 65. 709-911 (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.,Itok,K. et al: "Melanocyte Lysis by CTL Recognizing the MART-1 Melanoma Antigen in HLA-A2 Patients with Voot-Koyanagi-Harada (VKH) Disease." Int. Immunol.8. 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] Iwamoto,O.,Itoh,K., et al.: "Detection of MAGE-4 protein in sera of patients with head and neck squamous cell carclnoma." Int. J. Can.(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] Itoh,K.,Hayashi,H.,et al: "In : International Reviews of Immunology" (eds) Kumagai,K.,Kasakura,S.,Springer-Verlag. New York. (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] Takahashi, K., Shichijo, S., Noguchi, M., Hirohata, M., Itoh K: "Identification of MAGE-1 and -4 proteins in spermatogonia and primary spermatocytes of testis" Cancer Res. 55. 3478-3482 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakao, M., Yamana, H., Imai, Y., Toh, Y., Toh, U., Kimura, A., Yanoma, S., Kakegawa, T., Itoh, K: "HLA A2601-restricted cytotoxic T lymphocytes recognizing a peptide antigen expressed on squamous cell carcinoma" Cancer Res. 55. 4248-4252 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shichijo, S., Sagawa, K., Brasseur, T., and Itoh, K: "MAGE-1 gene is expressed in T cell leukemia" (Letter), Int. J.Cancer. 65. 709-711 (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., Shichijo, S., Ito, K: "Melanocyte Lysis by CTL Recognizing the MART-1 Melanoma Antigen in HLA-A2 Patients with Vogt-Koyanagi-Harada (VKH) Disease" Int. Immunol. 8. 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] 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" JJCR. 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] Itoh, K., Hayashi, A., Nakao, M., Hoshino, T., Seki, N., Shichijo, S: "Human tumor rejection antigens MAGE" JB Review J.Biochom. 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., Itoh, K: "Detection of MAGE-4 protein in sera of patients with head and neck squamous cell carcinoma" Int. J.Can. (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., Itoh, K.: "HLA-A locus-restricted and tumor-specific CTL in tumor infiltrating lymphocytes of patients with lung cancer" Cell. Immunol. 175. 101-110 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Gouhara, R., Nakao, M., Ogata, Y., Isomato, H., Oizumi, K., Itoh, K.: "Histocompatibility leukocyte antigen-2402-restricted cytotoxic T lymphocytes recognizing adenocarcinomas in tumor-infiltrating lymphocytes of patients with colon cancer" JJCR. 88. 198-204 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hoshino, T., Seki, N., Kikuchi, M., Kuramoto, T., Kodama, K., Koufuji, K., Iwamoto, O., Takeda, J., and Itoh, K: "HLA-classI-restricted and tumor-specific CTL in tumor-infiltrating lymphocytes of patients with gastric cancer" Int. C.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] Toh, U., Yamana, H., Nakao, M., Imai, Y., Seki, N., Takasu, H., Kaneshige, T., Fujita, H., Shirouzu, K., Itoh, K: "HLA-class-I-restricted and tumor-specific cytotoxic T lymphocytes from metastatic lymphocytes from metastatic lympho nodes of esophageal cancers" Cell. Immunol. (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, H., Nakao, M., Imai, Y., Yamada, A., Nishida, T., and Shichijo, S: Development of cancer vaccine by tumor rejection antigens. In : International Reviews of Immunology. (eds) Kumagai, K., Kasakura, S., Springer-Verlag, New York (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] Takahashi,K.,itoh K.et al.: "identification of MAGE-1 and-4 proteins in spermatogonia and primary spermatocytes of testis." Cancer Res.55. 3478-3482 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakao,M,itoh,k.et al.: "HLA A2601-restricted cytotoxic Tlymphocytes recognizing a peptlde antigen expressed on squamous cell carcinoma" Cancer Res.55. 4248-4252 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shichijo,S.,itoh,k.et al.: "Induction of MAGE genes in lymphold cells by the demethylating agent 5'-Aza-2'-deoxycytidine" JJCR. 87. 751-756 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shichijo,S.,itoh,k.et al.: "MAGE-1 gene is expressed in T cell leukemia." (Letter) ,lnt.J.Cancer.65. 709-711 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sugita,S,ltok,K.et al.: "Melanocyte Lysis by CTL Recognizing the MART-1Melanoma Antigen in HLA-A2 Patients with Voat-Koyanagi-Harada (VKH) Disease." int.immunol.8. 799-803 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] iwamoto,O.,itoh,K.,et al.: "Detection of MAGE-4 protein in sera of patients with head and neck squamous cell carcinoma." int,J.Can.(in press.). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] itoh,K.,Hayashi,H.,et al: "1997" (eds) Kumagai,K.,Kasakura,S.,Springer-Verlag,New York. (in press),

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

    • Related Report
      1995 Annual Research Report
  • [Publications] Shichijo, S.: "Establishment of an enzyme-linked immunosorbent assay (ELISA) for measuring cellular MAGE-4 protein on human cancers." J. Immunol. Meth.186. 137-149 (1995)

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

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

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakao, M.: "HLA A2601-restricted cytotoxic T lymphocytes recognizing a peptide antigen expressed on squamous cell carcinoma." Cancer Res.55. 4248-4252 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sugita, S.: "Melanocyte Lysis by CTL Recognizing the MART-1 Melanoma Antigen in HLA-A2 Patients with Vogt-Koyanagi-Harada (VKH) Disease." Int. Immunol.8 (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Itoh, K.: "Biology of Renal Cell Carcinoma" Ronald M. Bukowski, James H. Finke, Eric A. Klein, Springer-Verlag, (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Itoh, K.: "International Reviews of Immunology." (eds) Kumagai, K., Kasakura, S., Springer-Verlag (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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