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抗原提示能(ワクチン)細胞リソースとしての肺胞マクロファージ細胞融合の基礎的評価

Research Project

Project/Area Number 13877090
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionTohoku University

Principal Investigator

貫和 敏博  東北大学, 加齢医学研究所, 教授 (40129036)

Co-Investigator(Kenkyū-buntansha) 菊地 利明  東北大学, 医学部・附属病院, 助手 (10280926)
西條 康夫  東北大学, 医学部・附属病院, 助手 (10270828)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywords樹状細胞 / マクロファージ / 融合細胞ワクチン / 癌免疫療法 / 癌 / 免疫学 / 肺癌 / トランスレーリョナル リサーチ / 腫瘍免疫 / 細胞融合 / 腫瘍抗原 / 腫瘍ワクチン / allogenic
Research Abstract

抗原提示細胞と癌細胞との融合細胞を用いた癌免疫療法について、(1)融合細胞の効率の良い作成方法の確立、(2)抗原提示細胞として樹状細胞(DCs)とマクロファージ(MΦ)を用いた際の抗腫瘍効果について、さらに(3)抗原提示細胞としてsyngeneicとallogeneicの系における抗腫瘍効果について比較検討した。まず、融合細胞の作成方法としてポリエチレングリコールを用いる方法と電気融合法の両者でどちらの方法でも、約20〜30%の効率で作成することができた。また、融合細胞では癌細胞表面分子と抗原提示細胞の表面分子の両者の分子を発現することを確認できた。続いてin vivoの実験として、マウス大腸癌株C26を用い、syngeneic (Balb/c)とallogeneic (C57/BL6)のマウス骨髄由来DCsおよび腹腔MΦと電気融合させ、皮下にC26(5x10^5個)を接種したマウスに、3日目と10日目に融合細胞ワクチンを照射後に腹腔投与し、腫瘍の増殖抑制効果を検討した。その結果、PBS対照と比べた接種21日後の皮下腫瘍体積では(1)C26とallogeneic DCsの融合細胞ワクチン効果は64%の増殖抑制と最も強く(2)次にallogeneic MΦを用いた融合細胞ワクチンでは52%の抑制効果を示した。これに対し、(3)syngeneic DCsを使用した場合は42%、(4)syngeneic MΦを使用した場合は38%の抑制効果を示したのみであった。免疫後のマウス脾細胞からは同様の順の強さで癌細胞を殺傷するような細胞傷害性細胞を誘導することができた。本研究をもとに、更に強い抗腫瘍免疫効果を惹起できるように、サイトカイン遺伝子導入癌細胞(IL-12等)とDCsの融合細胞ワクチンを作成し評価する新たな研究課題を追求する。

Report

(2 results)
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Usui K, et al.: "N-terminal deletion augments the cell death inducing activity of BAX in adenoviral gene delivery to non-small cell lung cancers"Oncogene. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura A, et al.: "Increased susceptibility to LPS -induced endotoxin shock in secretory leukoprotease inhibitor (SLPI)-deficient mice"J. Exp. Med.. 197. 669-674 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimizukawa M, et al.: "Intratracheal gene transfer of decorin reduces subpleural fibroproliferation induced by bleomycin"Am. J. Physiol.. 284. L526-L532 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoue A, et al.: "Severe acute interstitial pneumonia and gefitinib"Lancet. 361. 137-139 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kikuchi T, et al.: "Tumor suppression induced by intratumor administration of adenovirus vector expressing NK4, a 4-kringle antagonist of hepatocyte growth factor, and naive dendritic cells"Blood. 100. 3950-3959 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hagiwara K, et al.: "Mouse SWAM1 and SWAM2 are antibacterial proteins composed of a single whey acidic protein motif"J. Immunol.. 170. 1973-1979 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Pradono P, Tazawa R, Maemondo M, Tanaka M, Usui K, Saijo Y, Hagiwaara K, Nukiwa T: "Gene transfer of thromboxane A(2) synthase and prostaglandin I(2) synthase antithetically altered tumor angiogenesis and tumor growth"Cancer Research. 62(1). 63-66 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Maemondo M, Narumi K, Saijo Y, Usui K, Tazawa R, Nakamura T, Nukiwa T: "Targeting Angiogenesis and HGF Function Using an Adenoviral Vector Expressing the HGF Antagonist NK4 for Cancer Therapy"Molecular Therapy. 5(2). 177-185 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishimoto O, Kawahara C, Enjo K, Obinata M, Nukiwa T, Ikawa S: "Gene transfer of thromboxane A(2) synthase and prostaglandin I(2) synthase antithetically altered tumor angiogenesis and tumor growth"Cancer Research. 62(3). 636-641 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kimura Y, Takahashi K, Totsune K, Darnel AD, Ebina M, Nukiwa T, Sasano H: "Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart"J Clin Endocrinol Metab. 87(1). 340-346 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kikuchi T, Hagiwara K, Gomi K, Kobayashi T, Takahashi H, Watanabe A, Nukiwa T: "Clarithromycin suppresses lipopolysaccharide (LPS)-madiated interleukin-8 (IL-8) production from human monocytes through AP-1 and NF-kB transcripition factors"Journal of Antimicrobial Chemotherapy. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki T, Fukuhara T, Tanaka M, Saijo Y, Kikuchi T, Tazawa R, Hagiwara K, Nukiwa T: "INDUCTION OF ANTITUMOR IMMUNITY BY FUSION OF ANCER CELLS WITH APCS : COMPARISON OF ALLOGENEIC VS.SYNGENEIC AND DENDRITIC CELLS VS.MACROPHAGES"American Association for Cancer Research 93rd Annual Meeting Proceedings. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 工藤翔二, 中田紘一郎, 貫和敏博: "呼吸器疾患最新の治療"南江堂. 467 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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