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Clinical application of NKT cell immune system for lung cancer

Research Project

Project/Area Number 15209045
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
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) TANIGUCHI Masaru  RIKEN, The Research Center for Immunology and Allergy, Director, 横浜研究所・免役・アレルギー科学総合研究センター, センター長 (80110310)
NAKAYAMA Toshinori  Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (50237468)
IIZASA Toshihiko  Chiba Cancer Center, Div, Thoracic Diseases, Executive Chief Surgeon, 呼吸器科, 主任医長 (10272303)
MOTOHASHI Shinichiro  Chiba University, Graduate School of Medicine, Research Associate Professor, 大学院医学研究院, 産官学連携研究員 (60345022)
尾辻 瑞人  千葉大学, 大学院・医学研究院, 助手 (50344982)
Project Period (FY) 2003 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥50,180,000 (Direct Cost: ¥38,600,000、Indirect Cost: ¥11,580,000)
Fiscal Year 2006: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2005: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2004: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2003: ¥21,710,000 (Direct Cost: ¥16,700,000、Indirect Cost: ¥5,010,000)
KeywordsNKT cell / dendritic cell / clinical trial
Research Abstract

We performed αGalactosylceramide-pulsed Dendritic cells in patients with lung cancer. Patients with advanced non-small cell lung cancer or recurrent lung cancer received intravenous injections of αGalCer-pulsed DCs (1x10^9/m^2) to test the safety, feasibility, and clinical response. Immunomonitoring was also performed in all completed cases. Eligible patients underwent peripheral blood leukapheresis, and peripheral blood mononuclear cells (PBMCs) were collected and further separated by density gradient centrifugation. PBMCs were cultured with human granulocyte-macrophage colony-stimulate factor (GM-CSF) for 1-2 weeks and pulsed with specific ligand, α-Galactosylceramide on the day before administration.
Seventeen patients were enrolled in this study. The frequency of peripheral blood NKT cells in all patients was measured by FACS analysis and IFN-γ production after restimulation with αGalCer in PBMCs was measured by ELISPOT assay. Patients with marked increase of FN-γ production following the administration of αGalCer-pulsed DC showed relatively long survival and time to tumor progression, while poor responder of IFN-γ production showed very poor prognosis. This is the first report to show the crucial role of IFN-γ at NKT cell immunotherapy. With these results, the role and mechanisms of IFN-γ production and anti-tumor immune response will be discussed.

Report

(5 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (34 results)

All 2006 2005 2004 Other

All Journal Article (34 results)

  • [Journal Article] Transbronchial fine needle aspiration cytological examination : a useful tool for diagnosing primary lung cancer.2006

    • Author(s)
      Iyoda A
    • Journal Title

      Thorac Cardiovasc Surg. 54・2

      Pages: 117-119

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Predictors of long-term survival with pulmonary metastasectomy for osteosarcomas and soft tissue sarcomas.2006

    • Author(s)
      Suzuki M
    • Journal Title

      J Cardiovasc Surg (Torino) 47・5

      Pages: 603-608

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Does perioperative high-dose prednisolone have clinical benefits for generalized myasthenia gravis?2006

    • Author(s)
      Sekine Y
    • Journal Title

      Eur J Cardiothorac Surg 29・6

      Pages: 908-913

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer.2006

    • Author(s)
      Suzuki M
    • Journal Title

      Cancer. 106・10

      Pages: 2200-2207

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Dose-volume factors predicting radiation pneumonitis in patients receiving salvage radiotherapy for postlobectomy locoregional recurrent non-small-cell lung cancer.2006

    • Author(s)
      Uno T
    • Journal Title

      Int J Clin Oncol. 11・1

      Pages: 55-59

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma : a morphological, immunohistochemical, and molecular analysis2006

    • Author(s)
      Hiroshima K
    • Journal Title

      Mod Pathol. 19・10

      Pages: 1358-1368

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Prognostic impact of large cell neuroendocrine histology in patients with pathologic stage Ia pulmonary non-small cell carcinoma.2006

    • Author(s)
      Iyoda A
    • Journal Title

      J Thorac Cardiovasc Surg. 132・2

      Pages: 312-315

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Comparison of endobronchial ultrasound, positron emission tomography, and CT for lymph node staging of lung cancer.2006

    • Author(s)
      Yasufuku K
    • Journal Title

      Chest. 132・3

      Pages: 710-718

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer.2006

    • Author(s)
      Motohashi S
    • Journal Title

      Clin Cancer Res. 2・20

      Pages: 6079-6086

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Prospective study of adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma.2006

    • Author(s)
      Iyoda A
    • Journal Title

      Ann Thorac Surg. 82・5

      Pages: 1802-1807

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Natural killer T cell-mediated antitumor immune responses and their clinical2006

    • Author(s)
      Seino K
    • Journal Title

      applications. Cancer Sci. 97・9

      Pages: 807-812

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Transbronchial fine needle aspiration cytological examination : a useful tool for diagnosing primary lung cancer.2006

    • Author(s)
      Iyoda A, Baba M, Shibuya K, Moriya Y, Yasufuku K, Sekine Y, Iizasa T, Hiroshima K, Nakatani Y, Fujisawa T.
    • Journal Title

      Thorac Cardiovasc Surg. 54(2)

      Pages: 117-119

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Predictors of long-term survival with pulmonary metastasectomy for osteosarcomas and soft tissue sarcomas.2006

    • Author(s)
      Suzuki M, Iwata T, Ando S, Iida T, Nakajima T, Ishii T, Yonemoto T, Tatezaki S, Fujisawa T, Kimura H.
    • Journal Title

      J Cardiovasc Surg (Torino) 47(5)

      Pages: 603-608

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Does perioperative high-dose prednisolone have clinical benefits for generalized myasthenia gravis?2006

    • Author(s)
      Sekine Y, Kawaguchi N, Hamada C, Sekiguchi H, Yasufuku K, Iyoda A, Shibuya K, Fujisawa T.
    • Journal Title

      Eur J Cardiothorac Surg 29(6)

      Pages: 908-913

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer.2006

    • Author(s)
      Suzuki M, Shigematsu H, Iizasa T, Hiroshima K, Nakatani Y, Minna JD, Gazdar AF, Fujisawa T.
    • Journal Title

      Cancer 106(10)

      Pages: 2200-2207

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dose-volume factors predicting radiation pneumonitis in patients receiving salvage radiotherapy for postlobectomy locoregional recurrent non-small-cell lung cancer.2006

    • Author(s)
      Uno T, Isobe K, Kawakami H, Ueno N, Kawata T, Yamamoto S, Sekine Y, Iyoda A, Iizasa T, Fujisawa T, Shigematsu N, Ito H.
    • Journal Title

      Int J Clin Oncol. 11(1)

      Pages: 55-59

    • NAID

      10020572345

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma : a morphological, immunohistochemical, and molecular analysis2006

    • Author(s)
      Hiroshima K, Iyoda A, Shida T, Shibuya K, Iizasa T, Kishi H, Tanizawa T, Fujisawa T, Nakatani Y.
    • Journal Title

      Mod Pathol. 19(10)

      Pages: 1358-1368

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prognostic impact of large cell neuroendocrine histology in patients with pathologic stage Ia pulmonary non-small cell carcinoma.2006

    • Author(s)
      Iyoda A, Hiroshima K, Moriya Y, Sekine Y, Shibuya K, Iizasa T, Nakatani Y, Fujisawa T.
    • Journal Title

      J Thorac Cardiovasc Surg. 132(2)

      Pages: 312-315

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comparison of endobronchial ultrasound, positron emission tomography, and CT for lymph node staging of lung cancer.2006

    • Author(s)
      Yasufuku K, Nakajima T, Motoori K, Sekine Y, Shibuya K, Hiroshima K, Fujisawa T.
    • Journal Title

      Chest. 130(3)

      Pages: 710-718

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer.2006

    • Author(s)
      Motohashi S, Ishikawa A, Ishikawa E, Otsuji M, Iizasa T, Hanaoka H, Shimizu N, Horiguchi S, Okamoto Y, Fujii S, Taniguchi M, Fujisawa T, Nakayama T.
    • Journal Title

      Clin Cancer Res. 2(20 Pt1)

      Pages: 6079-6086

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prospective study of adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma.2006

    • Author(s)
      Iyoda A, Hiroshima K, Moriya Y, Takiguchi Y, Sekine Y, Shibuya K, Iizasa T, Kimura H, Nakatani Y, Fujisawa T.
    • Journal Title

      Ann Thorac Surg. 82(5)

      Pages: 1802-1807

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Natural killer T cell-mediated antitumor immune responses and their clinical2006

    • Author(s)
      Seino K, Motohashi S, Fujisawa T, Nakayama T, Taniguchi M.
    • Journal Title

      Applications. Cancer Sci. 97(9)

      Pages: 807-812

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prospective study of adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma..2006

    • Author(s)
      Iyoda A
    • Journal Title

      Ann Thorac Surg. 82・5

      Pages: 1802-1807

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A phase I study of α-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer.2005

    • Author(s)
      Ishikawa A.
    • Journal Title

      Clinical Cancer Research 11・11

      Pages: 1910-1917

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dendritic cell maturation by CD11c T cells and Vα24^+ natural killer T-cell activation by α-galactosylceramide2005

    • Author(s)
      Ishikawa E.
    • Journal Title

      International Journal of Cancer 117・2

      Pages: 265-273

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A phase I study of α-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer.2005

    • Author(s)
      Ishikawa, A., Motohashi, S., Ishikawa, E., Fuchida, H., Higashino, K., Otsuji, M., Iizasa, T., Nakayama, T., Taniguchi, M., Fujisawa, T.
    • Journal Title

      Clin. Can. Res. 11(11)

      Pages: 1910-1917

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dendritic cell maturation by CD11c-T cells and Vα24^+ natural killer T-cell activation by α-Galactosylceramide.2005

    • Author(s)
      Ishikawa, E., Motohashi, S., Ishikawa, A., Ito, T., Uchida, T., Kaneko, T., Tanaka, Y., Horiguchi, S., Okamoto, Y., Fujisawa, T., Tsuboi, K., Taniguchi, M., Matsumura, A., Nakayama, T.
    • Journal Title

      Int. J. Cancer 117(2)

      Pages: 265-273

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A phase I study of α-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer.2005

    • Author(s)
      Ishikawa A. et al.
    • Journal Title

      Clinical Cancer Research 11・5

      Pages: 1910-1910

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Dendritic cell maturation by CD11c-T cells and Vα24+ natural killer T-cell activation by α-galactosylceramide2005

    • Author(s)
      Ishikawa E. et al.
    • Journal Title

      International Journal of Cancer 117・2

      Pages: 265-265

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Impaired IFN-γ production of Vα24 NKT cells in non-remitting sarcoidosis.2004

    • Author(s)
      Kobayashi, S
    • Journal Title

      Int. Immunol 16・2

      Pages: 215-222

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Impaired IFN-γ production of Vα24 NKT cells in non-remitting sarcoidosis.2004

    • Author(s)
      Kobayashi, S., Kaneko, Y., Seino, K., Yamada, Y., Motohashi, S., Koike, J., Sugaya, K., Kuriyama, T., Asano, S., Tsuda, T., Wakao, H., Harada, M., Kojo, S., Nakayama, T., Taniguchi, M.
    • Journal Title

      Int. Immunol. 16(2)

      Pages: 215-222

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Methylation and Gene Silencing of the Ras-Related GTPase Gene in Lung and Breast Cancers.

    • Author(s)
      Suzuki M
    • Journal Title

      Ann Surg Oncol. (In Press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Methylation and Gene Silencing of the Ras-Related GTPase Gene in Lung and Breast Cancers.

    • Author(s)
      Suzuki M, Shigematsu H, Shames DS, Sunaga N, Takahashi T, Shivapurkar N, Iizasa T, Minna JD, Fujisawa T, Gazdar AF.
    • Journal Title

      Ann Surg Oncol. (In Press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Methylation and Gene Silencing of the Ras-Related GTPase Gene in Lung and Breast Cancers.

    • Author(s)
      Suzuki M
    • Journal Title

      Ann Surg Oncol. (In Press)

    • Related Report
      2006 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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