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HLA-A2402拘束性肝癌特異的癌退縮抗原遺伝子の同定

Research Project

Project/Area Number 09770985
Research Category

Grant-in-Aid for Encouragement of Young Scientists (A)

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

Principal Investigator

中尾 真修  久留米大学, 医学部, 講師 (40258447)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywords肝細胞癌 / CTL / HLA-A2402 / 癌拒絶抗原
Research Abstract

HLA-A2402陽性の肝細胞癌(HCC)患者の腫瘍浸潤リンパ球(Tumor-Infiltrated Lymphocytes;TIL)を分離し、IL-2にて長期培養を行い、T細胞株を樹立した。このT細胞株は肝癌細胞株(HCC、胆管細胞癌及び肝芽腫)及びその他の組織型(扁平上皮癌や腺癌など)の癌細胞株に対する細胞傷害活性を検討したところ、HCCのみならず一部の腺癌細胞株にも細胞傷害活性を示した。またHLA genotypeの明らかな細胞株をターゲットに対するキラー活性を解析した結果、この細胞傷害活性はHLA-A2402拘束性を示した。さらに、このT細胞株はナチュラル・キラー(NK)活性やlymphokine activated killer(LAK)活性を示さなかった。以上の結果より樹立したT細胞株はHLA-A2402拘束性にHCC及び腺癌の細胞上に発現している癌拒絶抗原を認識していることが示唆された。
樹立したHLA-A2402拘束性キラーT細胞株(Cytotoxic T lymphocytes;CTL)株より約5×10^9個のCTLの大量培養に成功した。大量培養したCTLは樹立したCTLと同様にHLA-A2402拘束性の細胞傷害活性を示した。今後は、このCTLを用いてHLA-A2402拘束性HCC特異的拒絶抗原遺伝子クローニングを行う予定である。現在、ターゲット細胞としてこのCTLの細胞傷害活性の最も感受性の高い癌細胞を検索しており、この細胞よりcDNAライブラリーを作製する予定である。

Report

(2 results)
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Kikuchi,M.,Nakao,M.,et al.: "Identification of a SART-1-derived peptoide capable of inducing the HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes." Int.J.Cancer,. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shichijo,S.,Nakao,M.,et al.: "Gann Monograph on Cancer Research No.48" Japan Scientific Societies Press,Tokyo(in press), (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyajima,J.et al.: "Higher suscepyibility of erythropoietin-producing renal cell carcinomas to lysis by lymphokine-activated killer cells." J.Immunother.Vol.19. 399-404 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Gohara,R.et al.: "HLA-A2402-restricted cytotoxic T lymphocytes recognizing adenocarcinoma in Tumor-infiltratinglymphocytes of patients with colon cancer." Jpn.J.Cancer Res.Vol.88. 198-204 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Uhi,T.et al.: "HLA class I-restricted tumor-specific cytotoxic T lymphocytes from metastatic lymph nodes of esophageal cancers." Cell.Immunol.Vol.177. 137-143 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakao,M.et al.: "CD4^+ hepatic cancer-specific Cytotoxic T lymphocytes in patients with hepatocellular carcinoma." Cell.Immunol.Vol.177. 176-181 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suekane,S.et al.: "HLA-A2-restricted and tumor specific cytotoxic T lymphocytes from tumor-infiltrating lymphocytes of a patient with testicular embyonal cancer." Jpn.J.Cancer Res.Vol.88. 1181-1189 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Schichijo,S.et al.: "A gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes." J.Exp.Med.Vol.187. 277-288 (1998)

    • Related Report
      1997 Annual Research Report

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

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