Invariant NKT cell-target immunotherapy for non-smallc cell lung cancer

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591808
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Chiba University
• Principal Investigator: MOTOHASHI Shinichiro 千葉大学, 大学院・医学研究院, 准教授 (60345022)
• Project Period (FY): 2009 – 2011
• Keywords: NKT細胞 / 免疫細胞療法 / 肺癌

Research Abstract

To clarify the anti-tumor mechanisms of NKT cells, immune responses in the surgically resected lung cancer sample and trans-bronchially collected tumor specimens were analyzed. As a results, a dramatic infiltration of activated iNKT cells, decreased expression of CD1d, increased IFN-γ production and decreased TGF-β level was observed in the tumor microenvironment after NKT cell-target treatment.

Research Products

• [Journal Article] Identification of a new organic anion transporting polypeptide 1B3m RNA isoform primarily expressed in human cancerous tissues and cells. Biochem (2012)
  • Author(s): Nagai, M., Furihata, T., Matsumoto, S., Ishii, S., Motohashi, S., Yoshino, I., Ugajin, M., Miyajima, A., Matsumoto, S., Chiba, K
  • Journal Title: Biophys. Res. Commun Volume: 418(4) Pages: 818-823
  • Peer Reviewed
• [Journal Article] Murine Schnurri-2 controls Natural Killer cell function and lymphoma development (2012)
  • Author(s): Yamashita, J., Iwamura, C., Mitsumori, K., Hosokawa, H., Sasaki, T., Takahashi, M., Tanaka, H., Kaneko, K., Hanazawa, A., Watanabe, Y., Shinoda, K., Tumes, D., Motohashi, S., Nakayama, T
  • Journal Title: Leuk. Lymphoma Volume: 53(3) Pages: 479-486
  • DOI: DOI:10.3109/10428194.2011.625099
  • Peer Reviewed
• [Journal Article] Memory type 2 helper Tcells induce long-lasting antitumor immunity by activating natural killer cells (2011)
  • Author(s): Kitajima, M., Ito, T., Tumes, DJ., Endo, Y., Onodera, A., Hashimoto, K., Motohashi, S., Yamashita, M., Nishimura, T., Ziegler, SF., Nakayama, T
  • Journal Title: Cancer Res Volume: 71(14) Pages: 4790-8
  • URL: http://cancerres.aacrjournals.org/content/71/14/4790.long
  • Peer Reviewed
• [Journal Article] Anti-tumor immune responses induced by iNKT cell-based immunotherapy for lung cancer and head and neck cancer (2011)
  • Author(s): Motohashi, S., Okamoto, Y., Yoshino, I., Nakayama, T
  • Journal Title: Clin Immunol Volume: 140(2) Pages: 167-76
  • DOI: DOI:10.1016/j.clim.2011.01.009
  • Peer Reviewed
• [Journal Article] Inductionof NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy (2011)
  • Author(s): Yamasaki, K., Horiguchi, S., Kurosaki, M., Kunii, N., Nagato, K., Hanaoka, H., Shimizu, N., Ueno, N., Yamamoto, S., Taniguchi, M., Motohashi, S., Nakayama, T., Okamoto, Y
  • Journal Title: Clin. Immunol Volume: 138(3) Pages: 255-265
  • DOI: DOI:10.1016/j.clim.2010.11.014
  • Peer Reviewed
• [Journal Article] Migration and immunological reaction after the administration ofα GalCer-pulsed antigen-presenting cells into the submucosa of patients with head and neck cancer (2011)
  • Author(s): Kurosaki, M., Horiguchi, S., Yamasaki, K., Uchida, Y., Motohashi, S., Nakayama, T., Sugimoto, A., Okamoto, Y
  • Journal Title: CancerImmunol. Immunother Volume: 60(2) Pages: 207-215
  • DOI: DOI:10.1007/s00262-010-0932-z
  • Peer Reviewed
• [Journal Article] A set of genes associated with the interferon-γ response of lung cancer patients undergoing α-galactosylceramide-pulsed dendritic cell therapy (2010)
  • Author(s): Okita, K., Motohashi, S., Shinnakasu, R., Nagato, K., Yamasaki, K., Sato, Y., Kitamura, H., Hijikata, A., Yamashita, M., Shimizu, K., Fujii, S., Ohara, O., Taniguchi, M., Sakaida, I., Nakayama, T
  • Journal Title: Cancer Sci Volume: 101(11) Pages: 2333-2340
  • DOI: DOI:10.1111/j.1349-7006.2010.01696.x
  • Peer Reviewed
• [Journal Article] Application of NKT cells in immunotherapy (2010)
  • Author(s): Ishii, Y. Motohashi, S. Shimizu K. Nakayama, T. Taniguchi, M. Fujii, S
  • Journal Title: Curr. Immunol. Rev Volume: 6 Pages: 109-115
  • Peer Reviewed
• [Journal Article] Adjuvant activity mediated by iNKT cells (2010)
  • Author(s): Fujii. S., Motohashi. S., Shimizu. K., Nakayama. T., Yoshiga. Y., Taniguchi. M
  • Journal Title: Semin. Immunol Volume: 22(2) Pages: 97-102
  • DOI: 10.1016/j.smim.2009.10.002}
  • Peer Reviewed
• [Journal Article] Molecular Characterization of Chronic Obstructive Pulmonary Disease-Related Non-Small Cell Lung Cancer Through Aberrant Methylation and Alterations of EGFR Signaling (2010)
  • Author(s): Suzuki, M., Wada, H., Yoshino, M., Tian, L., Shigematsu, H., Suzuki, H., Alaa, M., Tamura, H., Fujiwara, T., Nagato, K., Motohashi, S., Moriya, Y., Hoshino, H., Yoshida, S., Shibuya, K., Hiroshima, K., Nakatani, Y. Yoshino, I
  • Journal Title: Ann Surg Oncol Volume: 17(3) Pages: 878-888
  • DOI: DOI:10.1245/s10434-009-0739-3
  • Peer Reviewed
• [Journal Article] CD69 controls the pathogenesis of allergic airway inflammation (2009)
  • Author(s): Miki. M. T., Hasegawa. A., Iwamura. C., Shinoda. K., Tofukuji. S., Watanabe. Y., Hosokawa. H., Motohashi. S. Hashimoto. K., Shirai. M., Yamashita. M., Nakayama. T
  • Journal Title: J. Immunol Volume: 183(12) Pages: 8203-8215
  • DOI: DOI:10.4049/jimmunol.0900646
  • Peer Reviewed
• [Journal Article] Enhanced Th2 cell differentiation and allergen-induced airway inflammation in Zfp35-deficient mice (2009)
  • Author(s): Kitajima. M. Iwamura. C., Miki. H. T., Shinoda. K., Endo. Y., Watanabe. Y., Shinnakasu. R., Hosokawa. H., Hashimoto. K., Motohashi. S., Koseki. H., Ohara. O., Yamashita. M., Nakayama. T
  • Journal Title: J. Immunol Volume: 183(8) Pages: 5388-5396
  • DOI: DOI:10.4049/jimmunol.0804155
  • Peer Reviewed
• [Journal Article] Invariant natural killer T cell-based immunotherapy for cancer (2009)
  • Author(s): Motohashi. S., Nakayama. T
  • Journal Title: Immunotherapy Volume: 1(1) Pages: 73-82
  • DOI: DOI:10.2217/1750743X.1.1.73
  • Peer Reviewed
• [Journal Article] Natural killer T cell-mediated immunotherapy for malignant diseases (2009)
  • Author(s): Motohashi. S., Nakayama. T
  • Journal Title: Frontiers in Bioscience Volume: S1(1) Pages: 108-116
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/19482686
  • Peer Reviewed
• [Journal Article] Prostaglandin E2 receptor 2 overexpression in squamous cell carcinoma of the lung correlates with p16INK4A methylation and an unfavorable prognosis (2009)
  • Author(s): Alaa, M., Suzuki, M., Yoshino, M., Tian, L., Suzuki, H., Nagato, K., Fujiwara, T., Wada, H., Moriya, Y. Hoshino, H., Motohashi, S., Yoshida, S., Shibuya, K., Hiroshima, K., Nakatani, Y., Abdrabou, A., Elkholy, M., Mahfouz, T., Yoshino, I
  • Journal Title: Int J Oncol Volume: 34(3) Pages: 805-812
  • DOI: DOI:10.3892/ijo_00000206
  • Peer Reviewed
• [Journal Article] Combination therapy of in vitro-expandednatural killer T cells and α-galactosylceramide-pulsed antigen-presenting cells in patients with recurrent head and neck carcinoma (2009)
  • Author(s): Kunii, N., Horiguchi, S., Motohashi, S., Yamamoto, H., Ueno, N., Yamamoto, S., Sakurai, D., Taniguchi, M., Nakayama, T., Okamoto, Y
  • Journal Title: Cancer Sci Volume: 100(6) Pages: 1092-1098
  • DOI: DOI:10.1111/j.1349-7006.2009.01135.x
  • Peer Reviewed
• [Journal Article] Aphase I-II study of α-Galactosylceramide(KRN7000)-pulsed IL-2/GM-CSF-cultured peripheral blood mononuclear cells in patients with advanced and recurrentnon-small cell lung cancer (2009)
  • Author(s): Motohashi, S., agato, K., Kunii, N., Yamamoto, H., Yamasaki, K., Okita, K., Hanaoka, H., Shimizu, N., Suzuki, M., Yoshino, I., Taniguchi, M., Fujisawa, T., Nakayama, T
  • Journal Title: J. Immunol Volume: 182(4) Pages: 2492-2501
  • DOI: DOI:10.4049/jimmunol.0800126
  • Peer Reviewed
• [Journal Article] Accumulation of activated invariant natural killer T cells in the tumor microenvironment after α-Galactosylceramide-pulse dantigen presenting cells
  • Author(s): Nagato, K., Motohashi, S., Ishibashi, F., Okita, K., Yamasaki, K., Moriya, Y., Hoshino, H., Yoshida, S., Hanaoka, H., Fuji, S., Taniguchi, M., Yoshino, I., Nakayama, T
  • Journal Title: J. Clin. Immunol. Volume: (in press)
  • Peer Reviewed
• [Presentation] 進行期および再発非小細胞肺癌に対するα-GalCerパルス抗原提示細胞の局所投与療法ー第I相試験 (2011)
  • Author(s): 石橋史博, 本橋新一郎, 谷口克, 吉野一郎, 中山俊憲
  • Organizer: 第40回日本免疫学会学術総会
  • Place of Presentation: 千葉市
  • Year and Date: 2011-11-27
• [Presentation] Immunotherapy using iNKTcells (2011)
  • Author(s): 本橋新一郎
  • Organizer: 第40回日本免疫学会学術総会
  • Place of Presentation: 千葉市
  • Year and Date: 2011-11-27
• [Presentation] 進行期および再発非小細胞肺癌に対するαGalCerパルス樹状細胞の局所的投与療法 (2011)
  • Author(s): 石橋史博, 本橋新一郎, 稲毛輝長, 森本淳一, 坂入祐一, 千代雅子, 米谷卓郎, 岩田剛和, 守屋康充, 溝渕輝明, 星野英久, 吉田成利, 吉野一郎
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2011-11-04
• [Presentation] 原発性肺癌に対するNKT細胞を標的とした免疫細胞治療 (2011)
  • Author(s): 本橋新一郎, 石橋史博, 谷口克, 吉野一郎, 中山俊憲
  • Organizer: 第70回日本癌学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-03
• [Presentation] NKT cell-based Immunotherapy for non-small cell lung cancer (2011)
  • Author(s): Motohashi. S., Ishibashi. F., Taniguchi. M., Yoshino. I., Nakayama. T.
  • Organizer: 6th International Symposium on CD1 and NKT cells
  • Place of Presentation: Chicago/USA
  • Year and Date: 2011-09-24
• [Presentation] Trans-bronchial intratumoral injection of α-GalCer-pulsed APCs in patiants with advanced or recurrent lung cancer (2011)
  • Author(s): 石橋史博, 本橋新一郎, 谷口克, 吉野一郎, 中山俊憲
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2011-06-30
• [Presentation] NKT細胞免疫系をターゲットにしたがんの免疫細胞治療 (2011)
  • Author(s): 中山俊憲, 本橋新一郎
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2011-06-30
• [Presentation] 進行期および再発非小細胞肺癌に対するαGalCerパルス樹状細胞の局所投与療法(第I相試験) (2011)
  • Author(s): 石橋史博, 本橋新一郎, 坂入祐一, 田村創, 和田啓伸, 岩田剛和, 守屋康充, 溝渕輝明, 星野英久m 岡本龍郎m 吉田成利, 吉野一郎
  • Organizer: 第28回日本呼吸器外科学会
  • Place of Presentation: 別府市
  • Year and Date: 2011-05-13
• [Presentation] NKT cell-based Immunotherapy for lung cancer (2010)
  • Author(s): 本橋新一郎, 石橋史博, 谷口克, 中山俊憲, 吉野一郎
  • Organizer: 第48回日本癌治療学会学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2010-10-29
• [Presentation] Trans-bronchial injection of alpha-GalCer-pulsed APCs in patients with advanced or recurrent lung cancer (2010)
  • Author(s): Ishibashi. F., Motohashi. S., Taniguchi. M., Yoshino. I., Nakayama. T.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-22
• [Presentation] iNKT cell based immunotherapy for cancer (2010)
  • Author(s): Nakayama. T., Motohashi. S.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-22
• [Presentation] Trans-bronchial injectionofα-GalCer-pulsed APCs in patients with advanced or recurrentlungcancer. (2010)
  • Author(s): Ishibashi. F., Motohashi. S., Taniguchi. M., Yoshino. I., Nakayama. T.
  • Organizer: 第14回日本がん免疫学会総会
  • Place of Presentation: 熊本市
  • Year and Date: 2010-07-22
• [Presentation] 進行期および再発非小細胞肺癌に対するαGalCerパルス樹状細胞の局所投与療法(第I 相試験) (2010)
  • Author(s): 石橋史博, 本橋新一郎, 坂入祐一, 田村創, 和田啓伸, 芳野充, 守屋康充, 溝渕輝明, 星野英久, 岡本龍郎, 吉田成利, 鈴木実, 吉野一郎
  • Organizer: 第33回日本呼吸器内視鏡学会
  • Place of Presentation: 横浜市
  • Year and Date: 2010-06-09
• [Presentation] NKTcell-based Immunotherapy for lungcancer-Strategies to establish the effective adjuvant therapy (2010)
  • Author(s): 本橋新一郎
  • Organizer: afterradical treatment-NIRS-Chiba University G-COE Joint Symposium on Carbon-Ion Therapy and Immunotherapy
  • Place of Presentation: 千葉市
  • Year and Date: 2010-01-15
• [Presentation] NKT 細胞療法によるインターフェロンγ産生増強および生存期間延長に相関するバイオマーカーの検討 (2009)
  • Author(s): 本橋新一郎, 沖田幸祐, 山崎一樹, 長門芳, 土方敦司, 北村浩, 藤井眞一郎, 吉野一郎, 谷口克, 中山俊憲
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-02
• [Presentation] A set of genes whose expression is associated with the IFN-γ response/survival undergoing NKT cell-based immunotherapy (2009)
  • Author(s): Motohahsi. S., Okita. K., Yamasaki. K., Ishibashi. F., Fujii. S., Yoshino. I., Taniguchi. M., Nakayama. T.
  • Organizer: 第68回日本癌学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-10-01
• [Presentation] Promoter hypermethylation of p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers (2009)
  • Author(s): Yoshino, M., Suzuki, M., Moriya, Y., Hoshino, H., Motoahashi, S., Yoshida, S., Shibuya, K., Yoshino, I
  • Organizer: 13th World Conference on Lung Cancer
  • Place of Presentation: San Francisco/U.S.A.
  • Year and Date: 2009-09-28
• [Presentation] α-Galactosylceramide-pulsed antigen presenting cell treatment in patients with advanced NSCLC (2009)
  • Author(s): Motohashi, S., Nagato, K., Taniguchi, M., Nakayama, T., Yoshino, I.
  • Organizer: 13th World Conference on Lung Cancer
  • Place of Presentation: San Francisco/U.S.A.
  • Year and Date: 2009-07-31
• [Presentation] NKT cell immunotherapy for lungcancer (2009)
  • Author(s): 本橋新一郎, 長門芳, 吉野一郎, 谷口克, 中山俊憲
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 北九州市
  • Year and Date: 2009-06-24
• [Presentation] NKT 細胞を用いた肺癌に対する免疫細胞療法 (2009)
  • Author(s): 本橋新一郎
  • Organizer: 第26回日本呼吸器外科学会総会
  • Place of Presentation: 北九州市
  • Year and Date: 2009-05-14
• [Presentation] がんに対するNKT細胞免疫系を用いた免疫細胞療法 (2009)
  • Author(s): 本橋新一郎
  • Organizer: お茶の水がん学アカデミア第54回集会
  • Place of Presentation: 東京都
  • Year and Date: 2009-04-13
• [Book] Clinical trials of invariant Natural Killer Tcell-based immunotherapy for cancer (2011)
  • Author(s): Motohashi, S., Okamoto, Y., Nakayama, T.
  • Total Pages: 185-198
  • Publisher: Edited by Berzofsky and Terabe
• [Book] Natural Killer T cells : Blancing the Regulation of Tumor Immunity (2011)
  • Author(s): Taniguchi, M., Fujii, S., Nakayama, T., Motohashi, S., Dashtsoodal, N., Watarai, H., Harada, M.
  • Total Pages: 1-14
  • Publisher: Edited by Berzofsky and Terabe
• [Book] 免疫細胞療法;がんの湿潤・転移.臨床と基礎 (2011)
  • Author(s): 本橋新一郎, 中山俊憲
  • Total Pages: 73-79
  • Publisher: 南山堂
• [Book] NKT 細胞免疫療法;がん免疫療法-実用化へのチャレンジ- (2010)
  • Author(s): 本橋新一郎, 中山俊憲
  • Total Pages: 129-134
  • Publisher: シーエムシー出版
• [Book] NKT 細胞免疫療法のトランスレーショナルリサーチ;くすりとからだ (2010)
  • Author(s): 本橋新一郎, 中山俊憲
  • Total Pages: 344-347
  • Publisher: 日本薬理学雑誌
• [Remarks] 千葉大学大学院医学研究院免疫発生学
  • URL: http://www.m.chiba-u.ac.jp/class/meneki/
• [Patent(Industrial Property Rights)] NKT細胞リガンドをパルスした抗原提示細胞による抗腫瘍療法の有効性の予測方法 (2009)
  • Inventor(s): 本橋新一郎
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 特許、特願2009-200911
  • Filing Date: 2009-08-31