• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

ムチン分子を標的とした上皮性腫瘍の免疫遺伝子療法

Research Project

Project/Area Number 12217097
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionYamaguchi University

Principal Investigator

日野田 裕治  山口大学, 医学部, 教授 (10165128)

Co-Investigator(Kenkyū-buntansha) 山本 光太郎  山口大学, 医学部, 助手 (50304481)
濱中 裕一郎  山口大学, 医学部, 助教授 (40189618)
萱野 幸三  山口大学, 医学部, 助手 (90314799)
石田 禎夫  札幌医科大学, 医学部, 助手 (20305220)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥57,800,000 (Direct Cost: ¥57,800,000)
Fiscal Year 2004: ¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2003: ¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2002: ¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2001: ¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2000: ¥12,000,000 (Direct Cost: ¥12,000,000)
KeywordsRHAMM / mRNA / dendritic cells / MHC class II / cancer immunotherapy / 樹状細胞 / TRP2 / B16 / EGFP / EL4 / ELISPOT / 免疫遺伝子療法 / MUC1 / ペプチドワクチン / CTL / リポソーム / 膵癌 / O-glycan / GalNAc transferase
Research Abstract

RHAMM (receptor for hyaluronan-mediated motility) mRNAを腫瘍抗原として樹状細胞療法の基礎的検討を行った。本mRNAはマウスの5種類の腫瘍細胞全てで発現していたが、正常組織では胸腺を除いて発現を認めなかった。RHAMMは細胞質内蛋白であるため、MHC class IIによる提示効率を高める目的でTRP-2との融合mRNAを作成した。RHAMM mRNA導入樹状細胞で免疫したマウスの脾細胞には明らかな殺細胞活性が誘導された。この誘導効果は抗CD4抗体投与で消失したが、抗CD8抗体は影響しなかった。EL4皮卞腫瘍(3日モデル)に対しても顕著な増殖抑制効果が観察されたが、この場合も抗CD8抗体ではなく、抗CD4抗体投与によってのみ治療効果が消失した。これらの結果から、本治療モデルにおいてはCD4+T細胞が抗腫瘍効果を発揮していることが示唆された。mRNA導入樹状細胞の臨床試験については、GMP基準準拠のcell processing center (CPC)で実施すべく手順書の作成が順調に進んでいる。さらに、胃癌および大腸癌において、細胞株・臨床検体のいずれにおいても高率にclass II transactivator (CIITA)遺伝子のメチル化が生じていることを明らかにした。このメチル化は5-azacytidineなどの脱メチル化剤によって解除できることから、class II陰性腫瘍のうちCIITAのメチル化が証明される場合は、脱メチル化剤併用免疫療法が有効である可能性がある。

Report

(5 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (24 results)

All 2004 Other

All Journal Article (5 results) Publications (19 results)

  • [Journal Article] Therapeutic effect of dendritic cells loaded with a fusion mRNA encoding tyrosinase-related protein 2 and enhanced green fluorescence protein on B16 melanoma.2004

    • Author(s)
      Fukui M. et al.
    • Journal Title

      Tumor Biol. 25

      Pages: 252-257

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Monoclonal antibodies as effective therapeutic agents for solid tumors.2004

    • Author(s)
      Hinoda Y. et al.
    • Journal Title

      Cancer Sci. 95

      Pages: 621-625

    • NAID

      80016809427

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The current status and issues concerning monoclonal antibody therapy.2004

    • Author(s)
      Hinoda Y.
    • Journal Title

      Bull.Yamaguchi Med.School 51

      Pages: 41-50

    • NAID

      120000863927

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Epigenetic inactivation -of class II transactivator (CIITA) is associated with the absence of interferon-gamma-induced HLA-DR expression in colorectal and gastric cancer cells.2004

    • Author(s)
      Satoh A. et al.
    • Journal Title

      Oncogene 23

      Pages: 8876-8886

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Epigenetic inactivation of the SFRP's complements genetic alterations to allow constitutive WNT pathway signaling in human colorectal cancer.2004

    • Author(s)
      Suzuki H. et al.
    • Journal Title

      Nature Genet. 36

      Pages: 417-422

    • Related Report
      2004 Annual Research Report
  • [Publications] Okano K. et al.: "Evaluation of a mRNA lipofection procedure for human dendritic cells and induction of cytotoxic T lymphocytes against enhanced green fluorescence protein."Tumor Biol.. 24. 317-324 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hamanaka Y. et al.: "Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer."Int.J.Cancer.. 103. 97-100 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hinoda Y. et al.: "Increased expression of MUC1 in advanced pancreatic cancer."J.Gastroenterol.. 38. 1162-1166 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nohara H. et al.: "Association between the interleukin-1 receptor antagonist polymorphism and ulcerative colitis with younger age at diagnosis."Immunol.Lett.. 90. 53-57 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki H. et al.: "Epigenetic inactivation of the SFRP's complements genetic alterations to allow constitutive WNT pathway signaling in human colorectal cancer."Nature Genet.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hamanaka T. et al.: "Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer. 103:97-100, 2003"Int. J. Cancer. 103. 97-100 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kodama H et al.: "Specific and effective targeting cancer immunotherapy with a combination of three bispecific antibodies"Immunology Lett. 81. 99-106 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoh Y et al.: "Expression of CD66a in multiple myeloma"J. Clin. Lab. Anal.. 16. 79-85 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okayama N et al.: "Simple genotype analysis of the Asp299Gly polymorphism of the Toll-like receptor-4 gene that is associated with lipopolysaccharide hyporesponsiveness"J. Clin. Lab. Anal.. 16. 56-58 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nohara H et al.: "Polymorphisms of the IL-1β and IL-1β-inducible genes in Ulcerative colitis"J. Gastroenterol.. 37:Suppl XIV. 107-110 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hinoda Y et al.: "Association of Functional Polymorphisms of the Matrix Metalloproteinase (MMP)-1 and MMP-3 Genes with Colorectal Cancer"Int. J. Cancer. 102. 526-529 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kodama H. et al.: "Specific and effective targeting cancer immunotherapy with a combination of three bispecific antibodies"Immunology Lett.. 81. 99-106 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] McDermott K.M. et al.: "Overexpression of MUC1 reconfigures the binding properties of tumor cells"Int. J. Cancer. 94. 783-791 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kodama H. et al.: "Mutated SEA-D227A-conjugated antibodies greatly enhance antitumor activity against MUC1-expressing bile duct carcinoma"Cancer Immunol. Immunother.. 50. 539-548 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi T. et al.: "MUC1 Mucin core protein binds to the domain 1 of ICAM-1"Digestion. 63 Suppl. 87-92 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] McDermott KM et al.: "Overexpression of MUC1 reconfigures the binding properties of tumor cells."Int J Cancer. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hayashi T et al.: "MUC1 Mucin core protein binds to the domain 1 of ICAM-1."Digestion. 63 Suppl S1. 87-92 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hayashi T et al.: "Mucins and immune reactions to mucins in ulcerative colitis."Digestion. 63 Suppl S1. 28-31 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Satoh S et al.: "Enhancement of metastatic properties of pancreatic cancer cells by transfer of MUC1 gene encoding an anti-adhesion molecule."Int J Cancer. 88. 507-518 (2000)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi