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Development of novel immuno-gene therapy for gastrointestinal cancer using antigen presenting function of heat shock protein

Research Project

Project/Area Number 10671132
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKeio University

Principal Investigator

KITAGAWA Yuko  Keio University School of Medicine, Department of Surgery, Assistant Professor, 医学部, 助手 (20204878)

Co-Investigator(Kenkyū-buntansha) TODA Masahiro  Keio University School of Medicine, Institute for Advanced Medical Research Assistant Professor, 医学部, 助手 (20217508)
KAWAKAMI Yutaka  Keio University School of Medicine, Institute for Advanced Medical Research Professor, 医学部, 教授 (50161287)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsheat shock protein / gastrointestinal cancer / immuno-gene therapy / tumor rejection / antigen presentation / dendritic cell
Research Abstract

The anti-tumor effect of heat-shock proteins (hsp) derived from CMS7-ME tumor was investigated. CMS7-ME, cell line was established by a HER2/neu transduction into the CMS7 derived from BALB/c mice fibrosarcoma. Three kinds of hsps, gp-96, hsp-70, hsp-90 were extracted from CMS7-ME and subcutaneously inoculated into the other mice. CMS7-ME tumor was implanted into these hsp-immunized mice. In gp96 or hsp-70 treated group, growth inhibitory effect implanted of CMS7-ME was observed. There is no anti-tumor effect in hsp-90 treated group.
In the model of CT-26, N-nitroso-N-methylurethane induced BALB/c colonic tumor, an anti-tumor effect of CT-26 derived hsps was investigated, gp-96 derived from CT-26 showed growth inhibitory effect to CT-26 tumor. There is no growth inhibitory effect of CT-26 derived hsp-70 or hsp-90 treated groups. The complex of gp96 extracted from normal liver and CT-26 specific peptide, AH-1 showed anti-tumor effect in this model. However an induction of AH-1 specific cytotoxic T cells was not detected in this experiment.
Anti-tumor effect of dendritic cells (DC) pulsed with gp96 derived from CT-26 was compared with that of DC pulsed with AH-1. DC pulsed with gp96 derived from CT-26 showed more significant growth inhibitory effect to CT-26 tumor in comparison with AH-1 pulsed DC.
These results suggest that the role of tumor derived hsp in the antigen presenting process.
Further investigation would be required to confirm the mechanisms of these effects as a pre-clinical investigation.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 北川雄光 他: "転移性腫瘍に対する免疫療法・免疫遺伝子治療の現況と展望"臨床科学. 54(2). 203-208 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawakami, Y: "Immunotherapy using T cell defined tumor antigens for melanoma"Microbiol Immunol. 42(12). 803-813 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kiniwa Y, et al.: "Tumor antigens isolated from a patient with vitiligo and T-cell-infiltrated melanoma"Cancer Res.. 61. 7900-7907 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawakami Y, et al.: "Isolation of a new melanoma antigen, MAR-2, Containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes"Immunol.. 66(4). 2871-2877 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 河上 裕: "免疫を標的とした治療法"「病気の分子医学」シリーズバイオサイエンスの新世紀. 14. 181-195 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 河上 裕: "免疫系が認識するヒト腫瘍抗原"癌治療の新たな試み 新編II. 253-284 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 河上 裕: "抗腫瘍免疫"実験医学別冊「Bio Science新用語ライブラリー 免疫 第2版」. 242-244 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 河上 裕: "樹状細胞を標的とした免疫療法"樹状細胞 基礎から臨床へ. 116-122 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 河上 裕: "腫瘍免疫機構と腫瘍抗原 -T細胞認識ヒト腫瘍抗原-"造血の再生医学と細胞療法. 1208-1218 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 河上 裕: "癌に対する細胞・免疫治療の現況"別冊・医学のあゆみ 免疫疾患-state of arts. 2. 391-395 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 河上 裕: "がんと免疫"「生体防御:免疫と感染症」シリーズバイオサイエンスの新世紀. 13. 204-220 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawakami, Y: "Immunotherapy using T cell defined tumor antigens for melanoma"Microbiol lmmnunol.. 42(12). 803-813 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kiniwa Y, Fujita T, Akada M, Ito K, Shofuda T, Suzuki Y, Yamamoto A, Saida T, and Kawakami Y: "Tumor antigens isolated from a patient with vitiligo and T-cell-infiltrated melanoma"Cancer Res.. 61. 7900-7907 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawakami Y, Wang X, Shofuda T, Sumimoto H, Tupesis JP, Fitzgerald E, Rosengerg SA: "Isolation of a new melanoma antigen, MAR-2, Containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes"Immunol.. 66(4). 2871-2877 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary

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Published: 1998-04-01   Modified: 2016-04-21  

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