Development of the novel molecular target therapy for the graft versus host disease (GVHD) using the humanized mice

• Project/Area Number: 24659176
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: University of Tsukuba
• Principal Investigator: SHIBUYA Kazuko 筑波大学, 医学医療系, 准教授 (00302406)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 分子標的 / 移植片対宿主病 / 骨髄移植 / ヒト化マウス / 免疫応答制御

Research Abstract

We have previously demonstrated that DNAM-1 plays an important role in the development of GVHD in a mouse model and is an ideal molecular target for therapeutic approaches to GVHD.
In this project, to investigate whether the administration of anti-human DNAM-1 antibodies ameliorates human GVHD, we have generated humanized mice expressing the human DNAM-1 ligand, CD155. For this experiment, we established 87 anti-human DNAM-1 monoclonal antibodies.

Research Products

• [Journal Article] Establishment and Characterization of a Novel Anti-DNAM-1 Monoclonal Antibody (2013)
  • Author(s): Yamashita Y, Abe F, Hirochika R, Tahara-Hanaoka S, Shibuya A, Shibuya K.
  • Journal Title: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Volume: 32(1) Issue: 1 Pages: 60-64
  • DOI: 10.1089/mab.2012.0083
  • Peer Reviewed
• [Journal Article] CD226 interaction with CD155 impacts on retention and negative selection of CD8 positive thymocytes as well as T cell differentiation to follicular helper cells in Peyer's Patches. (2013)
  • Author(s): Danisch S et. al.
  • Journal Title: Immunobiology Volume: 218 Issue: 2 Pages: 152-158
  • DOI: 10.1016/j.imbio.2012.02.010
  • Peer Reviewed
• [Journal Article] Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice (2012)
  • Author(s): Yoh K, Morito N, Ojima M, Shibuya K, Yamashita Y, Morishima Y, Ishii Y, Kusakabe M, Nishikii H, Fujita A, Matsunaga E, Okamura M, Hamada M, Suto A, Nakajima H, Shibuya A, Yamagata K, Takahashi S
  • Journal Title: Eur J Immunol Volume: 42 Issue: 8 Pages: 1999-2009
  • DOI: 10.1002/eji.201142250
  • Peer Reviewed
• [Journal Article] Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor. (2012)
  • Author(s): Nakahashi-Oda, C., Tahara-Hanaoka, S., Shoji, M., Okoshi, Y., Nakano-Yokomizo, T., Ohkohchi, N., Yasui, T., Kikutani, H., Honda, S., Shibuya, K., Nagata, S. and Shibuya, A.
  • Journal Title: J Exp. Med. Volume: 209 Issue: 8 Pages: 1493-1503
  • DOI: 10.1084/jem.20120096
  • Peer Reviewed
• [Journal Article] 急性GVHD発症における活性化免疫受容体DNAM-1の重要な役割 (2012)
  • Author(s): 金谷穣、鍋倉宰、渋谷和子、渋谷彰
  • Journal Title: 臨床血液 Volume: 53(5) Pages: 497-503
  • NAID: 130004501673
  • URL: http://ci.nii.ac.jp/naid/10030831285
• [Journal Article] Identification of phosphatidylserine as a ligand for the CD300a immunoreceptor (2012)
  • Author(s): Chigusa Nakahashi-Oda, et.al.
  • Journal Title: BBRC Volume: 417 Issue: 1 Pages: 646-650
  • DOI: 10.1016/j.bbrc.2011.12.025
  • Peer Reviewed
• [Presentation] Involvement of soluble CD155 in cancer immune escape (2013)
  • Author(s): Iguchi A, Shibuya A, Shibuya K.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2013-12-13
• [Presentation] Involvement of CD300a in the pathogenesis of DSS-induced colitis (2013)
  • Author(s): Totsuka N, Kim YG, Tahara-Hanaoka S, Nakahashi-Oda C, Honda S, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2013-12-13
• [Presentation] Fca/mR (CD351) regulates inflammatory responses of marginal zone B cells against experimental septic shock (2013)
  • Author(s): Honda S, Yoshizawa Y, Sato K, Fujimoto M, Nakahashi-Oda C, Tahara-Hanaoka S, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2013-12-12
• [Presentation] Critical role of DNAM-1 in acute and chronic allograft rejection (2013)
  • Author(s): Abe F, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2013-12-11
• [Presentation] A co-stimulatory molecule CD155 on CD4+ T Cells regulates allergic reactions by induction of interferon-γ-dependent th1 development (2013)
  • Author(s): Yamashita Y, Takahashi Y, Wang Y, Shibuya A, Shibuya K.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2013-12-11
• [Presentation] Soluble DNAX accessory molecule-1 (sDNAM-1) is a novel predictive biomarker for acute graft-versus-host disease (2013)
  • Author(s): Kanaya M, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2013-12-11
• [Presentation] CD155 is a co-stimulatory molecule involved in Th1 development (2013)
  • Author(s): Yamashita Y, Takahashi Y, Abe F, Shibuya A, Shibuya K.
  • Organizer: International Symposium Immune Regulation by Immunoreceptors
  • Place of Presentation: University of Tsukuba.(つくば)
  • Year and Date: 2013-04-12
• [Presentation] The role of an activating receptor, DNAM-1 (CD226), on small peritoneal macrophages (SPMs) (2013)
  • Author(s): Takenaka E, Shibuya A, Shibuya K.
  • Organizer: International Symposium Immune Regulation by Immunoreceptors
  • Place of Presentation: University of Tsukuba.(つくば)
  • Year and Date: 2013-04-12
• [Presentation] CD155 mediates a costimulatory signal for Th1 development and is involved in the development of allergic diseases (2013)
  • Author(s): Yamashita Y, Takahashi Y, Abe F, Shibuya A, Shibuya K.
  • Organizer: JST-CREST国際シンポジウムFrontiers in Immunology & Inflammation
  • Place of Presentation: 一橋記念講堂(東京)
  • Year and Date: 2013-02-12
• [Presentation] The paradoxical role of an immune receptor, DNAM-1, in tumor development (2013)
  • Author(s): Shibuya K.
  • Organizer: 第3回発がんスパイラル国際シンポジウム
  • Place of Presentation: 金沢エクセルホテル東急(金沢)
  • Year and Date: 2013-01-24
• [Presentation] Involvement of soluble CD155 in cancer immune escape. (2013)
  • Author(s): Iguchi A, Shibuya A, Shibuya K
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Involvement of CD300a in the pathogenesis of DSS-induced colitis. (2013)
  • Author(s): Totsuka N, Kim YG, Tahara-Hanaoka S, Nakahashi-Oda C, Honda S, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Fca/mR (CD351) regulates inflammatory responses of marginal zone B cells against experimental septic shock. (2013)
  • Author(s): Honda S, Yoshizawa Y, Sato K, Fujimoto M, Nakahashi-Oda C, Tahara-Hanaoka S, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Critical role of DNAM-1 in acute and chronic allograft rejection. (2013)
  • Author(s): Abe F, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] A co-stimulatory molecule CD155 on CD4+ T Cells regulates allergic reactions by induction of interferon-γ-dependent th1 development. (2013)
  • Author(s): Yamashita Y, Takahashi Y, Wang Y, Shibuya A, Shibuya K.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Soluble DNAX accessory molecule-1 (sDNAM-1) is a novel predictive biomarker for acute graft-versus-host disease. (2013)
  • Author(s): Kanaya M, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] The paradoxical role of an immune receptor, DNAM-1, in tumor development. (2013)
  • Author(s): Shibuya K
  • Organizer: 第3回発がんスパイラル国際シンポジウム
  • Place of Presentation: 金沢エクセルホテル東急（金沢）
  • Invited
• [Presentation] Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor (2012)
  • Author(s): Nakahashi-Oda C, Tahara-Hanaoka S, Yasui T, Kikutani H, Honda S, Shibuya K, Nagata S, Shibuya A.
  • Organizer: 第41回日本免疫学会国際シンポジウム
  • Place of Presentation: 神戸国際会議場(兵庫)
  • Year and Date: 2012-12-06
• [Presentation] CD155 is a co-stimulatory molecule involved in Th1 differentiation (2012)
  • Author(s): Yamashita Y, Takahashi Y, Wang Y, Abe F, Yoshioka A, Shibuya A, Shibuya K.
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場(兵庫)
  • Year and Date: 2012-12-05
• [Presentation] Critical role of DNAM-1 in acute and chronic allograft rejection (2012)
  • Author(s): Abe F, Shibuya K, Shibuya A.
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場(兵庫)
  • Year and Date: 2012-12-05
• [Presentation] CD155 mediates a costimulatory signal for Th1 development and is involved in the development of allergic diseases (2012)
  • Author(s): Yamashita Y, Takahashi Y, Abe F, Shibuya A, Shibuya K.
  • Organizer: The 7^<th> Tsukuba Medical Science Research Meeting
  • Place of Presentation: Tsukuba International Congress Center.(つくば)
  • Year and Date: 2012-10-01
• [Presentation] 活性化免疫受容体DNAM-1の急性肝GVHDの病態形成における重要な役割 (2012)
  • Author(s): 金谷穣、渋谷和子、阿部史枝、鍋倉宰、渋谷彰
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 金沢市文化ホール(金沢)
  • Year and Date: 2012-08-18
• [Presentation] 可溶型DNAM-1の急性GVHD発症予測マーカーとしての有用性 (2012)
  • Author(s): 金谷穣、広近玲、渋谷和子、岡田昌文、我妻ゆき子、坂巻壽、渋谷彰
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 金沢市文化ホール(金沢)
  • Year and Date: 2012-08-18
• [Presentation] CD155 (poliovirus receptor)のTh1分化における役割と疾患への関与 (2012)
  • Author(s): 山下由美、高橋勇一、王軼楠、吉岡文、鍋倉宰、渋谷彰、渋谷和子
  • Organizer: 第22回Kyoto T Cell Conference
  • Place of Presentation: 和順会館(京都)
  • Year and Date: 2012-07-07
• [Presentation] Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor (2012)
  • Author(s): Nakahashi-Oda C, Tahara-Hanaoka S, Shibuya K, Shibuya A.
  • Organizer: 9th International Conference on Innate Immunity
  • Place of Presentation: Rodos Palace Conference Center, Ixia, Rhodes, Greece
  • Year and Date: 2012-06-27
• [Presentation] Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor (2012)
  • Author(s): Nakhashi-Oda C
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会議場（兵庫）
  • Invited
• [Presentation] CD155 is a co-stimulatory molecule involved in Th1 differentiation (2012)
  • Author(s): Yamashita Y
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会議場（兵庫）
• [Presentation] Critical role of activating immune receptor DNAM-1 in the development of acute hepatic GVHD (2012)
  • Author(s): Kanaya M
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会議場（兵庫）
• [Presentation] Critical role of DNAM-1 in acute and chronic allograft rejection (2012)
  • Author(s): Abe F
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会議場（兵庫）
• [Presentation] CD155 (poliovirus receptor)のTh1分化における役割と疾患への関与 (2012)
  • Author(s): 山下 由美
  • Organizer: 第22回Kyoto T Cell Conference
  • Place of Presentation: 和順会館（京都）
• [Presentation] CD155 is a co-stimulatory molecule involved in Th1 development. International Symposium Immune Regulation by Immunoreceptors.
  • Author(s): Yamashita Y, Takahashi Y, Abe F, Shibuya A, Shibuya K.
  • Organizer: International Symposium Immune Regulation by Immunoreceptors.
  • Place of Presentation: University of Tsukuba.（つくば）
• [Presentation] The role of an activating receptor, DNAM-1 (CD226), on small peritoneal macrophages (SPMs).
  • Author(s): Takenaka E, Shibuya A, Shibuya K.
  • Organizer: International Symposium Immune Regulation by Immunoreceptors.
  • Place of Presentation: University of Tsukuba.（つくば）
• [Presentation] Small Peritoneal Macrophages (SPMs)上のDNAM-1の機能解析
  • Author(s): 竹中 江里
  • Organizer: 筑波大学・東京理科大学生命医科学研究所合同リトリート
  • Place of Presentation: 東京理科大学セミナーハウス（野田）
• [Presentation] CD155 is a co-stimulatory molecule involved in Th1 development
  • Author(s): 山下 由美
  • Organizer: 筑波大学・東京理科大学生命医科学研究所合同リトリート
  • Place of Presentation: 東京理科大学セミナーハウス（野田）
• [Presentation] 急性GVHDにおける活性化受容体DNAM-1の役割
  • Author(s): 金谷 穣
  • Organizer: Tsukuba Hematologic Disease Seminar第10回記念シンポジウム
  • Place of Presentation: つくば国際会議場（つくば）
• [Presentation] CD155 mediates a costimulatory signal for Th1 development and is involved in the development of allergic diseases
  • Author(s): Yamashita Y
  • Organizer: JST-CREST国際シンポジウムFrontiers in Immunology & Inflammation
  • Place of Presentation: 一橋記念講堂（東京）
• [Presentation] 可溶型DNAM-1の急性GVHD発症予測マーカーとしての有用性
  • Author(s): 金谷 穣
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 金沢市文化ホール（金沢）
• [Presentation] 活性化免疫受容体DNAM-1の急性肝GVHDの病態形成における重要な役割
  • Author(s): 金谷 穣
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 金沢市文化ホール（金沢）
• [Book] 細胞内染色法を用いたサイトカイン産生の解析, 実験医学別冊最強のステップUPシリーズ直伝!フローサイトメトリー面白いほど使いこなせる! (2014)
  • Author(s): 金丸由美、渋谷和子
  • Total Pages: 275
  • URL: https://www.yodosha.co.jp/jikkenigaku/book/9784758101882/index.html
• [Book] 実験医学別冊 最強のステップUPシリーズ 直伝！フローサイトメトリー 面白いほど使いこなせる！ (2014)
  • Author(s): 金丸 由美、渋谷 和子
  • Publisher: 羊土社
• [Book] 免疫細胞上の活性化受容体DNAM-1(CD226), 「生体の科学」 (2013)
  • Author(s): 竹中江里、渋谷和子、渋谷彰
  • Total Pages: 522
  • Publisher: 公益財団法人金原一郎記念医学医療振興財団(64(5))
  • URL: http://www.igaku-shoin.co.jp/journalDetail.do?journal=35200
• [Book] 公益財団法人金原一郎記念医学医療振興財団「生体の科学」 (2013)
  • Author(s): 竹中 江里、渋谷 和子、渋谷 彰
  • Publisher: 医学書院
• [Book] 免疫update （分担執筆：Th1、Th2、Th17～その発見から最近の知見まで～） (2012)
  • Author(s): 渋谷和子
  • Total Pages: 252
  • Publisher: 南山堂
• [Remarks] つくばリポジトリ
  • URL: http://www.tulips.tsukuba.ac.jp/dspace/simple-search?query=%E6%B8%8B%E8%B0%B7%E3%80%80%E5%92%8C%E5%AD%90&submit=%E6%A4%9C%E7%B4%A2
• [Remarks] TRIOS
  • URL: http://trios.tsukuba.ac.jp/researcher/0000001639
• [Patent(Industrial Property Rights)] 免疫疾患に対する医薬組成物 (2014)
  • Inventor(s): 渋谷 和子、渋谷 彰、山下 由美
  • Industrial Property Rights Holder: 渋谷 和子、渋谷 彰、山下 由美
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-03-13
• [Patent(Industrial Property Rights)] 免疫疾患に対する医薬組成物 (2014)
  • Inventor(s): 渋谷 和子、渋谷 彰、山下 由美
  • Industrial Property Rights Holder: 渋谷 和子、渋谷 彰、山下 由美
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-03-13
• [Patent(Industrial Property Rights)] 免疫疾患に対する医薬組成物 (2013)
  • Inventor(s): 渋谷 和子、渋谷 彰、山下 由美
  • Industrial Property Rights Holder: 渋谷 和子、渋谷 彰、山下 由美
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-03-13
• [Patent(Industrial Property Rights)] 同種間での移植心臓、移植血管、または移植腎臓の生着を維持するために用いられる薬剤 (2012)
  • Inventor(s): 渋谷 彰、渋谷 和子、阿部 史枝
  • Industrial Property Rights Holder: 渋谷 彰、渋谷 和子、阿部 史枝
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-05-23
• [Patent(Industrial Property Rights)] 同種間での移植心臓、移植血管、または移植腎臓の生着を維持するために用いられる薬剤 (2012)
  • Inventor(s): 渋谷 彰、渋谷 和子、阿部 史枝
  • Industrial Property Rights Holder: 渋谷 彰、渋谷 和子、阿部 史枝
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-05-23