Structural analysis of costimulatory molecules expressed on human γδ T cells

• Project/Area Number: 20590489
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: TANAKA Yoshimasa Kyoto University, 大学院・医学研究科, 特定准教授 (90280700)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: PD-1 / PD-L1 / 抗腫瘍効果 / T細胞 / T細胞受容体 / 非ペプチド性抗原 / テトラマー / IRp60 / X線結晶解析 / BirA / ストレプトアビジン / 免疫 / カラムクロマトグラフィー / 結晶 / タンパク質 / 大腸菌 / 二次構造 / モノクローナル抗体 / 抗原

Research Abstract

The extracellular domains of human PD-1 and PD-L1 molecules were expressed in E. coli as inclusion bodies and refolded. The refolded proteins were purified on anion-exchange column chromatography and gel filtration. IRp60, which is expressed on human γδ T cells, was similarly expressed and purified, then tetramerized. The tetramer revealed that the ligand of IRp60 was expressed on antigen-presenting cells.

Research Products

• [Journal Article] Phase I/II study of adoptive transfer of γδ T cells in combination with zoledronic acid and IL-2 to patients with advanced renal cell carcinoma (2011)
  • Author(s): Hirohito Kobayashi, Yoshimasa Tanaka, Junji Yagi, Nagahiro Minato, Kazunari Tanabe.
  • Journal Title: Cancer Immunol. Immunother. in press
• [Journal Article] A new indicator of a favorable prognosis in locally advanced renal cell carcinomas : γδ T-cells in peripheral blood (2011)
  • Author(s): Hirohito Kobayashi, Yoshimasa Tanaka, Hayakazu Nakazawa, Junji Yagi, Nagahiro Minato, Kazunari Tanabe.
  • Journal Title: Anticancer Res 31 Pages: 1027-1031
• [Journal Article] Dysregulated generation of follicular helper T cells in the spleen triggers fetal autoimmune hepatitis in mice (2011)
  • Author(s): Nobuhiro Aoki, Masahiro Kido, Satoru Iwamoto, Hisayo Nishiura, Ryutaro Maruoka, Junya Tanaka, Takeshi Watanabe, Yoshimasa Tanaka, Taku Okazaki, Tsutomu Chiba, Norihiko Watanabe.
  • Journal Title: Gastroenterology 140 Pages: 1322-1333
• [Journal Article] Involvement of CD56brightCD11c+ cells in IL-18-mediated expansion of human γδ T cells (2011)
  • Author(s): Junko Tsuda, Wen Li, Hiromichi Yamanishi, Hideyuki Yamamoto, Akico Okuda, Shuji Kubo, Zhifeng Ma, Nobuyuki Terada, Yoshimasa Tanaka, Haruki Okamura.
  • Journal Title: J.Immunol 186 Pages: 2003-2012
• [Journal Article] Expression and function of PD-1 in human γδ T cells that recognize phosphoantigens (2011)
  • Author(s): Masashi Iwasaki, Yoshimasa Tanaka, Hirohito Kobayashi, Kaoru Murata-Hirai, Hideto Miyabe, Tomoharu Sugie, Masakazu Toi, Nagahiro Minato.
  • Journal Title: Eur. J.Immunol. 41 Pages: 345-355
• [Journal Article] Expression and function of PD-1 in human γδ T cells that recognize phosphoantigens (2011)
  • Author(s): Iwawsaki, M., et al.
  • Journal Title: European Journal of Immunology Volume: 41 Pages: 345-355
  • Peer Reviewed
• [Journal Article] Involvement of CD56^<bright>CD11c^+ cells in IL-18-mediated expansion of human γδT cells (2011)
  • Author(s): Tsuda, J., et al.
  • Journal Title: The Journal of Immunology Volume: 186 Pages: 2003-2012
  • Peer Reviewed
• [Journal Article] Dysregulated generation of follicular helper T cells in the spleen triggers fetal autoimmune hepatitis in mice (2011)
  • Author(s): Aoki, N., et al
  • Journal Title: Gastroenterology Volume: (In press)
  • Peer Reviewed
• [Journal Article] A schizont-derived protein, TpSCOP, is involved in the activation of NF-κB in Theileria parva-infected lymphocytes (2010)
  • Author(s): Kyoko Hayashida, Masakazu Hattori, Ryo Nakao, Yoshimasa Tanaka, Jung-Yeon Kim, Noboru Inoue, Vishvanath Nene, Chihiro Sugimoto.
  • Journal Title: Mol. Biochem. Parasitol. 174 Pages: 8-17
• [Journal Article] Complete remission of lung metastasis following adoptive immunotherapy using activated autologous gammadelta T-cells in a patient with renal cell carcinoma (2010)
  • Author(s): Hirohito Kobayashi, Yoshimasa Tanaka, Hiroaki Shimmura, Nagahiro Minato, Kazunari Tanabe.
  • Journal Title: Anticancer Res. 30 Pages: 575-579
• [Journal Article] Anti-PD-1 antibody reduces CD4+ PD-1+ T cells and relieves the lupus-like nephritis of NZB/W F1 mice (2010)
  • Author(s): Shimpei Kasagi, Seiji Kawano, Taku Okazaki, Tasuku Honjo, Akio Morinobu, Saori Hatachi, Kenichiro Shimatani, Yoshimasa Tanaka, Nagahiro Minato, Shunichi Kumagai.
  • Journal Title: J.Immunol. 184 Pages: 2337-2347
• [Journal Article] Complete remission of lung metastasis following adoptive immunotherapy using activated autologous gammadelta T-cells in a patient with renal cell carcinoma (2010)
  • Author(s): Kobayashi, H., et al.
  • Journal Title: Anticancer Research 30 Pages: 575-579
  • Peer Reviewed
• [Journal Article] Anti-PD-1 antibody reduces CD4+PD-1- T cells and relieves the lupus-like nephritis of NZB/W F1 mice (2010)
  • Author(s): Kasagi, S., et al.
  • Journal Title: The Journal of Immunology 184 Pages: 2337-2347
  • Peer Reviewed
• [Journal Article] Rapid γδ TCR-mediated responses in γδ T cells transduced with cancer-specific TCR genes (2009)
  • Author(s): Atsunori Hiasa, Hiroyoshi Nishikawa, Michiko Hirayama, Shigehisa Kitano, Sachiko Okamoto, Hideto Chono, Seung Shin Yu, Junichi Mineno, Yoshimasa Tanaka, Nagahiro Minato, Ikunoshin Kato, Hiroshi Shiku.
  • Journal Title: Gene Therapy 16 Pages: 620-628
• [Journal Article] Rapid alphabeta TCR-mediated responses in gammadelta T cells transduced with cancer-specific TCR genes (2009)
  • Author(s): Hiasa, A., et al.
  • Journal Title: Gene Therapy 16 Pages: 620-628
  • Peer Reviewed
• [Journal Article] RapiαβTCR-mediated responses in γδ T cells transduced with cancer-specific TCR genes (2009)
  • Author(s): A Hiasa, et al.
  • Journal Title: Gene Therap
  • Peer Reviewed
• [Journal Article] Antitumor activity and some immunological properties of γδ T-cells from patients with gastrointestinal carcinomas (2008)
  • Author(s): Minoru Murayama, Yoshimasa Tanaka, Junji Yagi, Takehiko Uchiyama, Kenji Ogawa.
  • Journal Title: Anticancer Res 28 Pages: 2921-2931
• [Journal Article] The PD-1/PD-L1 complex resembles the antigen-binding Fvdomains of antibodies and T cell receptors (2008)
  • Author(s): D. Y. -W., Lin, et al.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. 105 Pages: 3011-3016
  • Peer Reviewed
• [Journal Article] Antitumor activity and some immunological properties of γδ T-cells from patients with gastrointestinal carcinomas (2008)
  • Author(s): M. Murayama, et al.
  • Journal Title: Anticancer Res. 28 Pages: 2921-2931
  • Peer Reviewed
• [Presentation] Structure-property relationships of cellulose ethers with regioselective and blockwise substituent patterns (2011)
  • Author(s): Hiroshi Kamitakahara, Atsushi Nakagawa, Arata Yoshinaga, Toshiyuki Takano, Tomoya Imai, Junji Sugiyama, Kaoru Hirai, Yoshimasa Tankaka, Frank Steiniger, Velina Sarbova, Dominik Fenn, Andreas Koschella, Thomas Heinze.
  • Organizer: 241^<st> ACS National Meeting & Exposition
  • Place of Presentation: Anaheim Convention Center, CA, U.S.A.
  • Year and Date: 2011-03-27
• [Presentation] Synthesis of amphiphilic tetrasachharides as drug carriers for hydrophobic compounds (2010)
  • Author(s): Hiroshi Kamitakahara, Kaoru Murata-Hirai, Yoshimasa Tanaka
  • Organizer: BIT's 1^<st> Annual World Congress of Nanomedicine 2010
  • Place of Presentation: Beijing International Convention Center, Beijing, China
  • Year and Date: 2010-10-23
• [Presentation] Synthesis and Cellular Uptake of Blockwise Alkylated Tetrasaccharide/ Hydrophobic Dye Complexes : Evaluation as Probes for a Novel Drug Delivery System (2010)
  • Author(s): Hiroshi Kamitakahara, Yoshimasa Tanaka
  • Organizer: The 25^<th> International Carbohydrate Symposium (ICS2010)
  • Place of Presentation: Makuhari Messe International Convention Complex, Chiba, Japan.
  • Year and Date: 2010-08-01
• [Presentation] Analysis of peripheral blood γδ T cells in patients with locally advanced renal cell carcinoma (2010)
  • Author(s): Yoshimasa Tanaka, Hirohito Kobayashi, Masashi, Iwasaki, Kazunari Tanabe, Nagahiro Minato
  • Organizer: 2010 γδ T cell conference
  • Place of Presentation: Kieler Schloss, Kiel, Germany
  • Year and Date: 2010-05-22
• [Presentation] Human γδ T cells : Application to cancer immunotherapy (2010)
  • Author(s): Tanaka, Y., et.al
  • Organizer: γδ T cell conference 2010
  • Place of Presentation: Kiel, Germany
• [Presentation] Phase I/II clinical trial of adoptive transfer of human γδ T cells in combination with zoledronate and IL-2 (2009)
  • Author(s): 湊長博, 田中義正, 小林博人, 田邉一成
  • Organizer: 第39回日本免疫学会学術総会
  • Place of Presentation: 大阪国際会議場大阪市大阪府
  • Year and Date: 2009-12-03
• [Presentation] Anti-PD-1 antibody reduces CD4+PD-1+ T cells and relieves the lupus-like nephritis of NZB/W (2009)
  • Author(s): Shimpei Kasagi, Seiji Kawano, Taku Okazaki, Tasuku Honjo, Akio Morinobu, Saori, Hatachi, Kenichiro Shimatani, Yoshimasa Tanaka, Nagahiro Minato, Shunichi Kumagai
  • Organizer: F1 mice. American College of Rheumatology Scientific Meeting 2009
  • Place of Presentation: Philadelphia, PA, U.S.A.
  • Year and Date: 2009-10-17
• [Presentation] Effect of PD-1/PD-L1 blockade on human γδ T cell recognition of tumors (2009)
  • Author(s): Masashi Iwasaki, Yoshimasa Tanaka, Nagahiro Minato
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜横浜神奈川県
  • Year and Date: 2009-10-02
• [Presentation] Effect of PD-1/PD-L1 blockade on human γδ T cell recognition of tumors (2009)
  • Author(s): Masashi Iwasaki, Yoshimasa Tanaka, Nagahiro Minato
  • Organizer: 2^<nd> European Congress of Immunology
  • Place of Presentation: International Congress Center Berlin, Berlin, Germany.
  • Year and Date: 2009-09-13
• [Presentation] γδ T cells and zoledronate : Application to cancer immunotherapy (2009)
  • Author(s): 田中義正
  • Organizer: Kyoto Breast Cancer Consensus Conference (KBCCC) 2009
  • Place of Presentation: Kyoto, Kyoto, Japan.
  • Year and Date: 2009-04-17
• [Presentation] Gammadelta T cells and zoledronate : Application to cancer immunotherapy (2009)
  • Author(s): Tanaka, Y.
  • Organizer: Kyoto Breast Cancer Consensus Conference 2009
  • Place of Presentation: Kyoto International Convention Center, Kyoto, Japan
  • Year and Date: 2009-04-17
• [Presentation] Human γδ T cells : Application to cancer immunotherapy (2009)
  • Author(s): 田中義正, 小林博人, 田邉一成, 湊長博
  • Organizer: Federation of Clinical Immunology Societies (FOCIS) 2009
  • Place of Presentation: San Francisco, CA, U.S.A.
• [Presentation] Derf2の構造解析と高次構造の変化に伴う抗原性変化 (2008)
  • Author(s): 田中義正
  • Organizer: 第45回日本小児アレルギー学会
  • Place of Presentation: パシフィコ横浜、横浜市、神奈川県
  • Year and Date: 2008-12-14
• [Presentation] Structural studies on PD-1/PD-L1 interactions (2008)
  • Author(s): Masashi Iwasaki, Yoshimasa Tanaka, Nagahiro Minato
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都国際会議場京都市京都府
  • Year and Date: 2008-12-03
• [Presentation] ヒトγδ型T細胞-基礎と臨床応用- (2008)
  • Author(s): 田中義正、小林博人、田邉一成、湊長博
  • Organizer: 第21回日本バイオセラピー学会学術集会総会
  • Place of Presentation: 東京ドームホテル、東京
  • Year and Date: 2008-11-19
• [Presentation] Human γδ T cells : Application to cancer immunotherapy (2008)
  • Author(s): 田中義正, 小林博人, 田邉一成, 湊長博
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場、名古屋市、愛知県
  • Year and Date: 2008-10-28
• [Presentation] Human γδ T cells : Application to cancer immunotherapy (2008)
  • Author(s): 田中義正
  • Organizer: Utano Summer Imunology Forum 2008
  • Place of Presentation: Uda, Nara, Japan
  • Year and Date: 2008-08-03
• [Presentation] ヒトγδ型T細胞の基礎的研究 (2008)
  • Author(s): 田中義正、小林博人、田邉一成、湊長博
  • Organizer: 第29回癌免疫外科研究会
  • Place of Presentation: ホテル日航、東京
  • Year and Date: 2008-06-20
• [Presentation] ヒトγδ型T細胞を利用した新規がん標識免疫療法の確立 (2008)
  • Author(s): 小林博人、田中義正、湊長博、田邉一成
  • Organizer: 第29回癌免疫外科研究会
  • Place of Presentation: ホテル日航、東京
  • Year and Date: 2008-06-20
• [Presentation] Dual Specificity of αβ-γδ TCR T cells : Transformation of Vγ9Vδ2 T cells with MAGE-A4 143-151-specific αβ type TCR genes (2008)
  • Author(s): Atsunori Hiasa, Hiroyoshi Nishikawa, Michiko Hirayama, Satiko Okamoto, Hideo Chono, Seung Shin Yu, Junichi Mineno, Yoshimasa Tanaka, Nagahiro Minato, Ikunoshin Kato, Hiroshi Shiku
  • Organizer: 第14回日本遺伝子治療学
  • Place of Presentation: 札幌医科大学、札幌市、北海道
  • Year and Date: 2008-06-12
• [Presentation] Human γδ T cells : Application to cancer immunotherapy (2008)
  • Author(s): 田中義正
  • Organizer: 2008 γδ T cell conference
  • Place of Presentation: Palais du Pharo, Marseille, France
  • Year and Date: 2008-05-23
• [Presentation] Human γδ T cells : Application to cancer immunotherapy (2008)
  • Author(s): Y. Tanakaa
  • Organizer: 2008 γδ T cell conference
  • Place of Presentation: Marseille, France
  • Year and Date: 2008-05-23
• [Book] ビスホスホン酸によるγδ型T細胞を標的とした乳癌免疫療法の開発(25(6)) (2010)
  • Author(s): 杉江知治、田中義正、岩崎雅史、戸井雅和、湊長博
  • Publisher: 乳癌の臨床
• [Book] ゾレドロン酸と乳癌抗腫瘍免疫(36(13)) (2009)
  • Author(s): 杉江知治、田中義正、戸井雅和
  • Publisher: Jpn.J.Cancer Chemother.
• [Book] アレルゲンの構造変化に伴う免疫応答の変調と免疫療法への応用(67(11)) (2009)
  • Author(s): 是松聖悟、田中義正
  • Publisher: 日本臨床
• [Book] Japanese Journal of Cancer and Chemotherapy (2009)
  • Author(s): 杉江知治, et al.
  • Total Pages: 5
  • Publisher: 癌と化学療法社
• [Book] 分子細胞生物学事典 第2版 (2008)
  • Author(s): 田中義正
  • Total Pages: 1184
  • Publisher: 東京化学同人
• [Remarks] ホームページ等
  • URL: http://www.ak.med.kyoto-u.ac.jp/
• [Remarks]
  • URL: http://www.ak.med.kyoto-u.ac.jp/
• [Patent(Industrial Property Rights)] 新規リンパ球処理剤 (2011)
  • Inventor(s): 田中義正
  • Industrial Property Rights Holder: 京都大学
  • Filing Date: 2011-01-27
• [Patent(Industrial Property Rights)] 新規リンパ球処理剤 (2009)
  • Inventor(s): 田中義正、湊長博
  • Industrial Property Rights Holder: 京都大学、アステラス製薬
  • Filing Date: 2009-07-09