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ヒト自家癌拒絶の免疫学的分子機構

Research Project

Project/Area Number 08266111
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionSapporo Medical University

Principal Investigator

菊地 浩吉  札幌医科大学, 医学部, 教授 (00045345)

Co-Investigator(Kenkyū-buntansha) 松浦 晃洋  札幌医科大学, 医学部, 助教授 (70157238)
古川 圭子  三重大学, 医学部, 助手 (50260732)
益子 高  東北大学, 薬学部, 助教授 (30157200)
別宮 好文  東京医科学研究所, 助手 (70199454)
笠原 正典  北海道大学, 医学部, 助教授 (30241318)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 1996: ¥10,200,000 (Direct Cost: ¥10,200,000)
Keywords人癌特異抗原 / 自家癌 / キラーT細胞クローン / T細胞抗原レセプター / 胃癌抗原 / 原癌遺伝子 / イムノプロテアソーム / 癌関連糖鎖
Research Abstract

癌の特異的免疫治療を目指し、人癌特異抗原を同定し、その自家T細胞による免疫学的認識、拒絶の分子機構を明らかにし自家癌拒絶の誘導法の開発を試みた。
1.癌患者リンパ球から、自家胃癌、膵癌、口腔癌特異的キラーT細胞クローンおよびヘルパーT細胞クローンを樹立し、癌抗原提示分子が各々、HLA-A31、-A24、-DR^*08032であることを証明した。自家胃癌に対するCTL誘導能を有する結合ペプチドの画分を精製し、抗原ペプチド分子の同定に成功した。
2.ヒト胃癌、膵癌を特異的に障害するT細胞クローンの抗原レセプター遺伝子をT細胞株にトランスフェクトし、TCR分子の細胞表面発現を認め、更にこれが自家癌抗原を認識することを確かめた。
3.原癌遺伝子(C-erbB-2)産物のKd拘束性ペプチド感作により特異的CTLを誘導できた。
4.MC誘発肉腫CMS5に特異的なCTLcloneの認識する腫瘍抗原遺伝子を単離し、その産物が第136アミノ酸にK→Q変異を持つ変異型MAPkinase(ERK2)であることを明らかにした。
5.イムノプロテアソームβサブユニット・ペアをコードする遺伝子を単離し、その構造、染色体居在を明らかにした。
6.腫瘍細胞の臓器浸潤や血行性転位に関与する癌関連糖鎖を合成する糖転位酵素、シアリルトランスフェラーゼおよびフコシルトランスフェラーゼの発現をアンチセンスcDNA等を用い制御できることを、成人T細胞性白血病および大腸癌について示した。
7.2つのヒトメラノーマ特異的CTLクローンは、HLA-A2拘束性にメラノーマを認識し、同時にHLA非拘束性に一部のメラノーマ細胞に対して細胞傷害活性を示した。これらの2つの異なった認識は1つのTCRによってなされていることが明らかになった。

Report

(1 results)
  • 1996 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Tamura,Y.,Kikuchi,K.他: "Inhibition of natural killer cell cytotoxicity by cell growth-related molecules." Jpn.J.Cancer Res.87. 623-630

    • Related Report
      1996 Annual Research Report
  • [Publications] Kamiguchi,K.,Kikuchi,K.他: "Non-MHC class I regulatory molecule for the cytotoxicity by natural killer cells." Art.Organs. 20. 862-865

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasoshima,T.,Kikuchi,K.他: "Estabilishment and characterization of human gastric carcinoma lines with high metastatic potential in the liver. Changes in integrin expression associated with the ability to metastasize in the liver of nude mice." Jpn.J.Cancer Res.87. 153-160

    • Related Report
      1996 Annual Research Report
  • [Publications] Takashima,S.,Kikuchi,K.他: "Interaction between cell-surface-expressed 70-kilodalton heat shock protein-like antigen and CD3^+4^-8^- killer T cells." Artificial Organs. 20. 857-861

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasoshima,T.,Kikuchi,K.他: "Changes in adhesion molecules expression associating with the ability of human gastric cancer cells to metastasize in the liver. In Tahara,E.,Sugimachi,K.and Oophara,T.Eds.,Recent Advances in Gastroenterological Carcinogenesis I,P."

    • Related Report
      1996 Annual Research Report
  • [Publications] Kasahara,M.,Ishibashi,T.他: "Chromosomal localization of the mouse proteasome Z subunit gene reveals an ancient chromosomal duplication involving the major histocompatibility complex." Proc.Natl.Acad.Sci.U.S.A.93. 9096-9101

    • Related Report
      1996 Annual Research Report
  • [Publications] Kandil,E.,Kasahara,M.他: "Isolation of low molecular mass polypeptide complementary DNA clones from primitive vertebrates : Implications for the origin of MHC class I-restricted antigen presentation." J.Immunol.156. 4245-4253

    • Related Report
      1996 Annual Research Report
  • [Publications] Kasahara,M.,Flajnik,M.F.他: "Origin and evolution of the class I gene family : Why are some of the mammalian class I genes encoded outside the major histocompatibility complex?" Res.Immunol.147. 278-284

    • Related Report
      1996 Annual Research Report
  • [Publications] Hayashi,M.,Kasahara,M.他: "Characterization of a human glycoprotein with a potential role in sperm-egg fusion : cDNA cloning,immunohistochemical localization,and chromosomal assignment of the gene (AEGL1)." Genomics. 32. 367-374

    • Related Report
      1996 Annual Research Report
  • [Publications] Beck,Y.,Takiguchi,M.他: "Dual recognition of a human cytotoxic T cell clone for melanoma antigens." Cancer Res.56. 2368-2374

    • Related Report
      1996 Annual Research Report
  • [Publications] Masuko,T.and Takeuchi,H.他: "Lipid structure of cytotoxic granules in living human killer Tlymphocytes studied by raman microspectoscopy. Biochim.Biophys." Acta in press.

    • Related Report
      1996 Annual Research Report
  • [Publications] Furukawa,K.,Aizawa,S.他: "Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides,but exhibit only subtle defects in their nervous system." Proc.Natl.Acad.Sci.USA. 93. 10662-10667

    • Related Report
      1996 Annual Research Report
  • [Publications] Furukawa,K.他: "Genomic organization and chromosomal assignment of the human β1,4-N-acetylgalactosaminyltransferase gene : Identification of multipletranscription units." J.Biol.Chem.271. 20836-20844

    • Related Report
      1996 Annual Research Report
  • [Publications] Furukawa,K,,他: "High expression of ganglioside GD3 synthase gene in adult T cell leukemia cells unrelated to the gene expression of human T lymphotropic virus type I." Cancer Res.56. 2844-2848

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsuyuoka,K.,and Kannagi,R.他: "Characterization of a T-Cell line specific to an anti-Id antibody related to the carbohydrate antigen,sialyl SSEA-1,and the immunodominat T-Cell antigenic site of the antibody." J.Immunol.157. 661-669

    • Related Report
      1996 Annual Research Report
  • [Publications] Narita,T.,Kannagi,R.他: "Alteration of integrins by heparin-binding EGF-like growth factor (HB-EGF) in human breast cancer cells." Oncology. 53. 374-381

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuura,A.,Kikuchi,K.他: "Clonal dominance of human autologous cytotoxic T lymphocytes against gastic carcinoma : Molecular stability of complimentarity determining region-3 structure of T cell receptor α/β gene." Int.Immunol.8. 75-82

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuura,A.,Fujimoto,J.他: "Inhibition of resistance to hemopoietic allografts in G-CSF transgenic mice." Eur.J.Immunol.26. 115-119

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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