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A immunotherapy for primary non small cell lung cancer with Vα24 NKT cells

Research Project

Project/Area Number 11357012
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Thoracic surgery
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

FUJISAWA Takehiko  Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (80110328)

Co-Investigator(Kenkyū-buntansha) IIZASA Toshihiko  Chiba University, University Hospital, Lecturer, 医学部付属病院, 講師 (10272303)
NAKAYAMA Toshinori  Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (50237468)
TANIGUCHI Masaru  Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (80110310)
MOTOHASHI Shinichirou  Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (60345022)
OTSUJI Mizuto  Chiba University, University Hospital, Assistant, 医学部付属病院, 助手 (50344982)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥38,480,000 (Direct Cost: ¥35,300,000、Indirect Cost: ¥3,180,000)
Fiscal Year 2002: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2001: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2000: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1999: ¥19,400,000 (Direct Cost: ¥19,400,000)
KeywordsNon Small Cell Lung Cancer / Metastasis / Dendritic cell / Immunotherapy / NKT cell / 肺癌 / 再発
Research Abstract

Primary lung cancer is hard to cure, even with intensive treatments. Approximately half or more of lung carcinoma patients, even those undergoing complete resection, had clinically undetectable local or distant micrometastases. Since intrapulmonary recurrence is commonly observed during postoperative follow-up of lung cancer, control of intrapulmonary metastases is particularly important for improving prognosis. We reported that α-GalCer-pulsed DCs activated Vαl4 NKT cells and eradicated established metastatic tumor foci in mouse lung metastasis models, and i.v.-injected α-GalCer-pulsed DCs reached to the lung and led to activation of endogenous Vα14 NKT cells. Equivalent amounts of Vα24 NKT cells appeared to exist in the human lung compared to Vα14 NKT cells in the mouse lung, and considerable numbers of Vα24 NKT cells infiltrated in the tumor tissue. This observation also suggests that the reduction of peripheral blood Vα24 NKT cell number is not a significant problem for clinical immunotherapy using α-GalCer-pulsed DCs. Here, we monitored the number of Vα14 NKT cells in the lung of mice receiving α-GalCer-pulsed DCs and found that significantly increased Vα24 NKT cells were sustained . Thus, we may expect similarly potent antitumor effects in humans when α-GalCer-pulsed DCs are administered. Our results suggest that micrometastasis in the lung of patients following radical surgery of cancer can be eradicated when α-GalCer-pulsed DCs are administered. We determined the precise conditions for clinical, application, α-GalCer-pulsed DC therapy might become a new' immunotherapy for lung cancer patients.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Motohashi S, Kobayashi S, Ito T, Magara KK, Mikuni O, Kamada N, Iizasa T, Nakayama T, Fujisawa T, Taniguchi M.: "Preserved IFN-alpha production of circulating Valpha24 NKT cells in primary lung cancer patients"Int J Cancer. 102巻2号. 159-165 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 本橋新一郎, 石川亜紀, 中山俊憲, 谷口克: "αガラクトシルセラミドとNKT細胞療法"血液・腫瘍科. 45巻3号. 246-250 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 本橋新一郎, 小林誠一郎, 真柄久美子, 中山俊憲, 谷口克: "NKT細胞免疫系を用いた細胞免疫療法の臨床への応用"実験医学. 19巻18号. 2397-2401 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Motohashi S, Kobayashi S, Ito T, Magara KK, Mikuni O, Kamada N, lizasa T, Sakayama T, Pujisawa T, Taniguchi M.: "Preserved IFN-alpha production of circulating Valpha24 NKT cells in primary lung cancer patients"Int J Cancer. 102. 159-165 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Taniguchi M, and Nakayama T.: "Recognition and function of Va14NKT cells"Sem Immunol. 12. 543-550 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawano T, Nakayama T, Kamada N, Kaneko Y, Harada M, Ogura N, Akutsu Y, Motohashi S, lizasa T, Endo H, Fujisawa T, Shinkai H, Taniguchl M.: "Anti-tumor cytotoxicity mediated by ligand-activated human Va24 NKT cells"Cancer Res. 59. 5102-5105 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Motohashi S, Kobayaski S, Ito T, Magara KK, Mikuni O, Kamada N, Iizasa T, Nakayama T, Fujisawa T, Taniguchi M: "Preserved IFN-alpha production of circulating Valpha24 NKT cells in primary lung cancer patients"Int J Cancer. 102巻2号. 159-165 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 本橋新一郎, 石川亜紀, 中山俊憲, 谷口克: "αガラクトシルセラミドとNKT細胞療法"血液・腫瘍科. 45巻3号. 246-250 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 本橋新一郎, 小林誠一郎, 真柄久美子, 中山俊憲, 谷口克: "NKT細胞免疫系を用いた細胞免疫療法の臨床への応用"実験医学. 19巻18号. 2397-2401 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] kawano T., et al.: "Anti-tumor cytotoxicity mediated by ligand-activated human Vα24 NKT cells"Cancer Research. 59. 5102-5105 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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