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細胞性免疫の誘導に基づく免疫療法

Research Project

Project/Area Number 09255106
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

高橋 利忠  愛知県がんセンター, 副所長 (00124529)

Co-Investigator(Kenkyū-buntansha) 佐藤 昇志  札幌医科大学, 医学部, 教授 (50158937)
安保 徹  新潟大学, 医学部, 教授 (30005079)
栗林 景容  三重大学, 医学部, 教授 (10064578)
河上 裕  慶応大学, 医学部, 教授 (50161287)
安元 公正  産業医科大学, 第二外科, 教授 (30150452)
菊地 浩吉  札幌医科大学, 医学部, 教授 (00045345)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥75,000,000 (Direct Cost: ¥75,000,000)
Fiscal Year 1999: ¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 1998: ¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 1997: ¥25,000,000 (Direct Cost: ¥25,000,000)
Keywords免疫療法 / NK1.1^+T細胞 / 細胞傷害性T細胞 / マウスTL抗原 / ウイルス誘発マウス腫瘍抗原 / ヒト胃癌抗原 / ヒト肺癌抗原 / ヒトメラノーマ抗原 / NK1.1 T細胞 / 細胞性免疫 / NK1.1T細胞 / モロニ-ウイルス誘発腫瘍抗原
Research Abstract

(1)マウスTL抗原遺伝子導入マウス由来の樹状細胞を用い、同系マウスを免疫することにより、TL抗原陽性腫瘍の増殖抑制を誘導しえることを示した。また、TL拘束性を示す細胞傷害性T細胞(CTL)はTAP非依存性に発現しているTL抗原エピトープを認識していることを示した。
(2)フレンドウイルス誘発腫瘍、FBL・3特異的CTLの中からIL・2産生能が高いクローンを選択し、養子移入した。この様なクローンは効率よく腫瘍を拒絶すること、長期にわたり記憶細胞として抗腫瘍活性を発揮すること、が明らかとなった。
(3)マウス腹腔に腫瘍細胞を移植すると、マクロファージがIL・12産生し、この内因性IL・12がNK細胞及びNKT細胞による抗腫瘍効果を誘することを明らかとした。
(4)自家癌患者由来のエフェクターT細胞クローンを用い、次の3種の標的抗原エピトープの同定に成功した。ヒト滑膜肉腫のSYT・SSX融合遺伝子産物由来のHLA・A24拘束性ペプチド、傍腫瘍症候群にかかわるrecoverin蛋白質由来のHLA・A24拘束性ペプチド、及び扁平上皮癌のαエノラーゼ由来のHLA・DR8拘束性ペプチド。
(5)CD80(B7)遺伝子を導入した自家肺癌細胞株を9例から樹立しており、このうち8例で肺癌特異的CTLの誘導を試み、クローニングの結果、4例でクローンの樹立に成功した。抗原解析を行ない、核内因子NF・YCの変異蛋白がHLA・B^*5202拘束性CTLの標的抗原であることを示した。
(6)ヒトメラノーマに対するHLA・A1拘束性CTLを用いて自家腫瘍cDNA発現ライブラリーより、新規抗原(8B6)をコードするcDNAを単離した。エピトープは遺伝子の突然変異に由来する変異ペプチドにあることを示した。

Report

(3 results)
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Yazaki, M.: "A novel minor histocompatibility antigen recognized by HLA-A31 restricted cytotoxic T lymphocytes generated from HLA-identical bone marrow lymphocytes"Bone Marrow Transplant.. 24. 129-137 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsuda, K.: "Survival-promoting activity of IL-7 on IL-2 dependent cytotoxic T lymphocyte clones : Resultant induction of GI arrest"J. Immunol. Methods. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawamura, T.: "Protective effect of NK1.1^+T cells as well as NK cells against intraperitoneal tumors in mice"Gell. Immunol.. 193. 219-225 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki, K.: "Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31 restricted cytotoxic T lymphocytes"J. Immunol.. 163. 2783-2791 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Imahayashi, S.: "Tumor-infiltrating B cells-derived IgG recognizes tumor components in human lung cancer"Gancer Invest.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawakami, Y.: "Identification of human melanoma antigens recognized by tumor infiltrating T lymphocytes and their use for immunotherapy"Monograph on Cancer Res.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsujimura,K.: "Two types of anti-TL CTL clones with distinct target specificities:Differences in cytotoxic mechanisms and accessory molecule requirements" J.Immunol.160. 5253-5261 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uenishi,H.: "Overlapping epitopes of Friend murine leukemia virus gag-encoded leader sequence recognized by single cytotoxic T-lymphocyte clones" Immunol.Let.62. 33-38 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawamura,T.: "Critical role of NK1^+ T cells in IL-12-induced immune responses in vivo" J.Immunol.160. 16-19 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takenoyama,M.: "Autologous cytotoxic T lymphocytes against human lung adenocarcinoma recognize shared antigens presented by HLA-A24" Jpn.J.Cancer Res.89. 1-7 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hanagiri,T.: "Effect of interleukin-12 on the induction of cytotoxic T lymphocytes from the regional lymph node lymphocytes of patients with lung adenocarcicoma" Jpn.J.Cancer Res.89. 192-198 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawakami,Y.: "Identification of new melanoma epitopes on melanosomal proteins recognized by tumor infiltrating T lymphocytes restricted by HLA-A1,-A2,and -A3 alleles" J.Immunol.161. 6985-6992 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuji,K.: "Requirement of CD4 T cells for skin graft rejection against thymus leukemia (TL) antigen and multiple epitopes on the TL molecule recognized by CD4 T cells." J.Immunol.159. 159-166 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsujimura,K.: "Two types of anti-TL CTL clones with distinct target specificty : differences in cytotoxic mechanisms and accessory molecule requirement." J.Immunol.160(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Uenishi,H.: "Induction of crossreactivity in endogenous viral peptide non-reactive to FBL-3 tumor-specific helper T cell clones." Microbiol.Immunol. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Moroda,T.: "Self-reactive forbideen clones are confirmed to pathways of intermediate T cell receptor cell differentiation even under immunosuppressive conditions." Immunology. 91. 88-94 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyazaki,A.: "Cytotoxicity of histocompatibility leukocyte antigen-CR8-restricted CD4^+ killer T cells against human autologus squamous cell carcinoma." Jpn.J.Cancer Res.88. 191-197 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takenoyama,M.: "Autologous cytotoxic T lymphocytes against human lung adenocarcinoma recognize shared antigens presented by HLA-A24." Jpn.J.Cancer Res.89. 1-7 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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