Combined application of molecular-targeted therapy and NKT immunotherapy for hematological malignancy

• Project/Area Number: 20591160
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: SHIMIZU Kanako The Institute of Physical and Chemical Research, 免疫治療モデル開発研究ユニット, ユニットリーダー (20391980)
• Co-Investigator(Kenkyū-buntansha): FUJII Shinーichiro 独立行政法人理化学研究所, 免疫細胞移植戦略研究ユニット, ユニットリーダー (10392094)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: NKT細胞 / α-GalCer / 腫瘍細胞 / 自然免疫 / 獲得免疫

Research Abstract

We have been focusing on the development of anti-tumor vaccine using adjuvant activity of NKT cells, which is α-Galcer loaded tumor cells (Tumor/Gal). In current study, we evaluated the efficacy of combination of Tumor/Gal with anti-cancer drug or molecular-targeted therapy in hematological tumor models. We found the possibility of synergistic effect of these approaches.

Research Products

• [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. 101 Pages: 2333-2340
  • NAID: 10027833301
  • Peer Reviewed
• [Journal Article] Human leukemic cells loaded with alpha-galactosylceramide (alpha-GalCer) activate murine NKT cells in situ. (2010)
  • Author(s): Shimizu K, Hidaka M, Bickham K, Moriwaki M, Fujimoto K, Kawano F, Fujii S
  • Journal Title: Int J Hematol. 92 Pages: 152-160
  • Peer Reviewed
• [Journal Article] Murine induced pluripotent stem cells can be derived from and differentiate into natural killer T cells. (2010)
  • Author(s): Watarai H, Fujii S, Yamada D, Rybouchkin A, Sakata S, Nagata Y, Iida-Kobayashi M, Sekine-Kondo E, Shimizu K, Shozaki Y, Sharif J, Matsuda M, Mochiduki S, Hasegawa T, Kitahara G, Endo TA, Toyoda T, Ohara O, Harigaya K, Koseki H, Taniguchi M
  • Journal Title: J Clin Invest. 120 Pages: 2610-2618
  • Peer Reviewed
• [Journal Article] Induction of Th1-biased cytokine production by alpha-carba-GalCer, a neoglycolipid ligand for NKT cells. (2010)
  • Author(s): Tashiro T, Sekine-Kondo E, Shigeura T, Nakagawa R, Inoue S, Omori-Miyake M, Chiba T, Hongo N, Fujii S, Shimizu K, Yoshiga Y, Sumida T, Mori K, Watarai H, Taniguchi M
  • Journal Title: Int Immunol 22 Pages: 319-328
  • Peer Reviewed
• [Journal Article] Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Valpha14-Jalpha18 TCRalpha gene. (2010)
  • Author(s): Watarai H, Rybouchkin A, Hongo N, Nagata Y, Sakata S, Sekine E, Dashtsoodol N, Tashiro T, Fujii S, Shimizu K, Mori K, Masuda K, Kawamoto H, Koseki H, Taniguchi M
  • Journal Title: Blood. 115 Pages: 230-237
  • 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. 22 Pages: 97-102
  • Peer Reviewed
• [Journal Article] Application of NKT cells in immunotherapy. (2010)
  • Author(s): Ishii Y, Motohashi S, Shimizu K, Nakayama Taniguchi M, Fujii S
  • Journal Title: Curr Immunol Review 6 Pages: 109-115
• [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 Pages: 2333-2340
  • NAID: 10027833301
  • Peer Reviewed
• [Journal Article] Human leukemic cells loaded with alpha-galactosylceramide (alpha-GalCer) activate murine NKT cells in situ (2010)
  • Author(s): Shimizu K, Hidaka M, Bickham K, Moriwaki M, Fujimoto K, Kawano F, Fujii S
  • Journal Title: Int J Hematol Volume: 92 Pages: 152-160
  • Peer Reviewed
• [Journal Article] Murine induced pluripotent stem cells can be derived from and differentiate into natural killer T cells (2010)
  • Author(s): Watarai H, Fujii S, Yamada D, Rybouchkin A, Sakata S, Nagata Y, Iida-Kobayashi M, Sekine-Kondo E, Shimizu K, Shozaki Y, Sharif J, Matsuda M, Mochiduki S, Hasegawa T, Kitahara G, Endo TA, Toyoda T, Ohara O, Harigaya K, Koseki H, Taniguchi M.
  • Journal Title: J Clin Invest Volume: 120 Pages: 2610-2618
  • Peer Reviewed
• [Journal Article] Induction of Th1-biased cytokine production by alpha-carba-GalCer, aneoglycolipid ligand for NKT cells (2010)
  • Author(s): Tashiro T, Sekine-Kondo E, Shigeura T, Nakagawa R, Inoue S, Omori-Miyake M, Chiba T, Hongo N, Fujii S, Shimizu K, Yoshiga Y, Sumida T, Mori K, Watarai H, Taniguchi M.
  • Journal Title: Int Immunol Volume: 22 Pages: 319-328
  • Peer Reviewed
• [Journal Article] Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Valpha14-Jalpha18 TCRalpha gene. (2010)
  • Author(s): Watarai H, Rybouchkin A, Hongo N, Nagata Y, Sakata S, Sekine E, Dashtsoodol N, Tashiro T, Fujii S, Shimizu K, Mori K, Masuda K, Kawamoto H, Koseki H, Taniguchi M.
  • Journal Title: Blood Volume: 115 Pages: 230-237
  • 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 Pages: 97-102
  • Peer Reviewed
• [Journal Article] Application of NKT cells in immunotherapy. (2010)
  • Author(s): Ishii Y, Motohashi S, Shimizu K, Nakayama Taniguchi M, Fujii S.
  • Journal Title: Curr Immunol Review Volume: 6 Pages: 109-115
  • Peer Reviewed
• [Journal Article] Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Valpha14-Jalpha18 TCRalpha gene (2010)
  • Author(s): Watarai H, Rybouchkin A, Hongo N, Nagata Y, Sakata S, Sekine E, Dashtsoodol N, Tashiro T, Fujii S, Shimizu K, Mori K, Masuda K, Kawamoto H, Koseki H, Taniguchi M.
  • Journal Title: Blood 115 Pages: 230-237
  • Peer Reviewed
• [Journal Article] DC therapy induces long-term NK reactivity to tumors via host DC. (2009)
  • Author(s): Shimizu K, Fujii S
  • Journal Title: Eur J Immunol. 39 Pages: 457-68
  • Peer Reviewed
• [Journal Article] Antigen mRNA-transfected, allogeneic fibroblasts loaded with NKT-cell ligand confer antitumor immunity. (2009)
  • Author(s): Fujii S, Goto A, Shimizu K
  • Journal Title: Blood. 113 Pages: 4262-4272
  • Peer Reviewed
• [Journal Article] Dendritic cell-based cancer immunotherapies. (2009)
  • Author(s): Fujii S, Takayama T, Asakura M, Aki K, Fujimoto K, Shimizu K
  • Journal Title: Arch Immunol Ther Exp. 57 Pages: 189-198
  • Peer Reviewed
• [Journal Article] Antigen mRNA-transfected, allogeneic fibroblasts loaded with NKT-cell ligand confer antitumor immunity (2009)
  • Author(s): Fujii S, Goto A, Shimizu K
  • Journal Title: Blood 113 Pages: 4262-4272
  • Peer Reviewed
• [Journal Article] Dendritic cell-based cancer immunotherapies (2009)
  • Author(s): Fujii S, Takayama T, Asakura M, Aki K, Fujimoto K, Shimizu K
  • Journal Title: Arch Immunol Ther Exp 57 Pages: 189-198
  • Peer Reviewed
• [Journal Article] 樹状細胞によるT細胞とNKT細胞への二重交差提示機能 (2009)
  • Author(s): 清水佳奈子、藤井眞一郎
  • Journal Title: 臨床免疫 51 Pages: 595-604
• [Journal Article] 自然免疫から獲得免疫への橋渡し (2009)
  • Author(s): 清水佳奈子、藤井眞一郎
  • Journal Title: 最新医学 64 Pages: 2371-2377
• [Journal Article] がん免疫療法-NKT細胞から獲得免疫へ (2009)
  • Author(s): 藤井眞一郎、清水佳奈子
  • Journal Title: 血液フロンテイア 19 Pages: 531-539
• [Journal Article] DC therapy induces long-term NK reactivity to tumors via host DC (2009)
  • Author(s): Shimizu K, Fujii S
  • Journal Title: European Journal of Immunology 39 Pages: 457-468
  • Peer Reviewed
• [Journal Article] An adjuvant role of in situ dendritic cells (DCs) in linking innate and adaptive immunity. (2008)
  • Author(s): Shimizu K, Fujii S.
  • Journal Title: Front Biosci. 13 Pages: 6193-201
  • Peer Reviewed
• [Journal Article] An adjuvant role of in situ dendritic cells (DCs) in linking innate and adaptive immunity (2008)
  • Author(s): Shimizu K, Fujii S
  • Journal Title: Frontier in Bioscience 13 Pages: 6193-6201
  • Peer Reviewed
• [Journal Article] NKT細胞と樹状細胞のクロストークを利用した免疫療法の新展開 (2008)
  • Author(s): 藤井眞一郎, 清水佳奈子
  • Journal Title: 実験医学 26 Pages: 196-204
• [Journal Article] NKT細胞による細胞免疫療法 (2008)
  • Author(s): 藤井眞一郎, 川口真喜子, 清水佳奈子
  • Journal Title: 血液・腫瘍科 57 Pages: 127-138
  • NAID: 40019064408
• [Journal Article] Adjuvant activity mediated by iNKT cells.
  • Author(s): Fujii S, Motohashi S, Shimizu K, Nakayama T, Yoshiga Y, Taniguchi M
  • Journal Title: Semin Immunol.
  • Peer Reviewed
• [Journal Article] Adjuvant activity mediated by iNKT cells
  • Author(s): Fujii S, Motohashi S, Shimizu K, Nakayama T, Yoshiga Y, Taniguchi M.
  • Journal Title: Semin Immunol (In press)
  • Peer Reviewed
• [Journal Article] 人工アジュバントベクター細胞の開発
  • Author(s): 清水佳奈子、朝倉三貴、藤井眞一郎
  • Journal Title: メデイカル・サイエンス・ダイジェスト (In press)
• [Journal Article] Antigen mRNA-transfected, allogeneic fibroblasts loaded with NKT cell ligand confer antitumor immunity
  • Author(s): Fujii S, Goto A, Shimizu K
  • Journal Title: Blood (印刷中)
  • Peer Reviewed
• [Presentation] Evaluation of long term NK reactivity to tumor generated by Dendritic cell therapy. (2010)
  • Author(s): 清水佳奈子
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe Japan
  • Year and Date: 2010-08-26
• [Presentation] Evaluation of long term NK reactivity to tumor generated by Dendritic cell therapy (2010)
  • Author(s): Kanako Shimizu
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-26
• [Presentation] 抗原mRNAとNKTリガンドを提示させたアジュバントベクター細胞による抗腫瘍効果の誘導 (2010)
  • Author(s): 清水佳奈子
  • Organizer: 第14回日本がん免疫学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2010-07-23
• [Presentation] 抗原mRNAとNKTリガンドを提示させたアジュバントベクター細胞による抗腫瘍効果の誘導 (2010)
  • Author(s): 清水佳奈子
  • Organizer: 第14回 日本がん免疫学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2010-07-23
• [Presentation] 抗原mRNAとNKTリガンドを提示させたアジュバントベクター細胞による抗腫瘍効果の誘導 (2010)
  • Author(s): 清水佳奈子
  • Organizer: 麒麟塾6th Kirin-Juku meeting
  • Place of Presentation: 東京
  • Year and Date: 2010-06-05
• [Presentation] 抗原mRNAとNKTリガンドを提示させたアジュバントベクター細胞による抗腫瘍効果の誘導 (2010)
  • Author(s): 清水佳奈子
  • Organizer: 麟麟塾6th Kirin-Juku meeting
  • Place of Presentation: 東京
  • Year and Date: 2010-06-05
• [Presentation] Dendritic cell therapy induces long term NK reactivity to tumors. (2009)
  • Author(s): 清水佳奈子
  • Organizer: 日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] Dendritic cell therapy induces long term NK reactivity to tumors (2009)
  • Author(s): 清水佳奈子
  • Organizer: 日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] Novel mode of action of DCs leading to long term NK cell reactivity to tumors. (2009)
  • Author(s): 清水佳奈子
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-23
• [Presentation] New Development of DC therapy. (2009)
  • Author(s): 清水佳奈子
  • Organizer: 日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23
• [Presentation] Novel mode of action of DCs leading to long term NK cell reactivity to tumors (2009)
  • Author(s): 清水佳奈子
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-23
• [Presentation] New Development of DC therapy (2009)
  • Author(s): 清水佳奈子
  • Organizer: 日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23
• [Presentation] ヒト腫瘍細胞を用いたNKT細胞療法への応用の考察 (2008)
  • Author(s): 清水佳奈子
  • Organizer: 第70回日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-11
• [Presentation] ヒト腫瘍細胞を用いたNKT細胞療法への応用の考察 (2008)
  • Author(s): 清水佳奈子
  • Organizer: 第70回日本血液学会
  • Place of Presentation: 京都・国際会議場
  • Year and Date: 2008-10-11
• [Book] 月刊メデイカル・サイエンス・ダイジェスト(癌の免疫療法 人工アジュバントベクター細胞の開発 36) (2010)
  • Author(s): 清水佳奈子、朝倉三貴、藤井眞一郎
  • Publisher: ニューサイエンス社
• [Book] 臨床免疫(樹状細胞によるT細胞とNKT細胞への二重交差提示機能 51) (2009)
  • Author(s): 清水佳奈子、藤井眞一郎
  • Publisher: 科学評論社
• [Book] 最新医学(自然免疫から獲得免疫への橋渡し 64) (2009)
  • Author(s): 清水佳奈子、藤井眞一郎
  • Publisher: 最新医学社
• [Book] 血液フロンテイア(がん免疫療法-NKT細胞から獲得免疫へ 19) (2009)
  • Author(s): 藤井眞一郎、清水佳奈子
  • Publisher: 医薬ジャーナル社
• [Book] 炎症と免疫(NKT細胞の新展開と臨床応用 16) (2008)
  • Author(s): 藤井眞一郎、本橋新一郎、清水佳奈子、安芸かおり、中山俊憲、谷口克
  • Publisher: 先端医学社
• [Book] 血液・腫瘍科(NKT細胞による細胞免疫療法 57) (2008)
  • Author(s): 藤井眞一郎、川口真喜子、清水佳奈子
  • Publisher: 科学評論社
• [Book] 実験医学(NKT細胞と樹状細胞のクロストークを利用した免疫療法の新展開 26) (2008)
  • Author(s): 藤井眞一郎、清水佳奈子
  • Publisher: 羊土社
• [Book] 炎症と免疫(NKT細胞の新展開と臨床応用 16) (2008)
  • Author(s): 藤井眞一郎,清水佳奈子
  • Publisher: 先端医学社