2006 Fiscal Year Final Research Report Summary
Clinical application of NKT cell immune system for lung cancer
| Project/Area Number |
15209045
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Chiba University |
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Principal Investigator |
FUJISAWA Takehiko Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (80110328)
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| 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)
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| Project Period (FY) |
2003 – 2006
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| Keywords | NKT cell / dendritic cell / clinical trial |
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| 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.
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Research Products
(30 results)
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[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.
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Journal Title
Cancer 106(10)
Pages: 2200-2207
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Int J Clin Oncol. 11(1)
Pages: 55-59
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Mod Pathol. 19(10)
Pages: 1358-1368
Description
「研究成果報告書概要(欧文)」より
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[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.
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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
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[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.
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Journal Title
Clin. Can. Res. 11(11)
Pages: 1910-1917
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Int. J. Cancer 117(2)
Pages: 265-273
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Int. Immunol. 16(2)
Pages: 215-222
Description
「研究成果報告書概要(欧文)」より
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