Analysis of HLA-DP-specific immune responses to develop a novel immunotherapy

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591415
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Nagoya University
• Principal Investigator: MURATA Makoto 名古屋大学, 医学部附属病院, 講師 (40378063)
• Project Period (FY): 2011 – 2013
• Keywords: 造血幹細胞移植 / HLA / Tリンパ球 / 抗体

Research Abstract

The 20-99% of leukemia cells was positive for HLA-DP expression. Twenty-four cytotoxic T cell (CTL) lines were isolated from blood obtained from seven patients who had received HLA-mismatched hematopoietic stem cell transplantation. All CTLs recognized HLA-class I or DR molecules but not DP molecule. Anti-HLA antibodies were detected in blood obtained from eight patients who had received multi-transfusion. All antibodies recognized HLA class I but not class II molecules. In vitro assay using patient serum containing anti-HLA antibody demonstrated that the hematopoietic stem cells were lysed by anti-HLA antibody through ADCC activity. Stimulation of T cells by .221 cells transfected with each HLA-DP cDNA construct is ongoing.

Research Products

• [Journal Article] Allogeneic transplantation for primary myelofibrosis with bone marrow, peripheral blood, or umbilical cord blood : An analysis of the JSHCT (2014)
  • Author(s): Murata M, Nishida T, Taniguchi S, Ohashi K, Ogawa H, Fukuda T, Mori T, Kobayashi H, Nakaseko C, Yamagata N, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Suzuki R, Naoe T
  • Journal Title: Bone Marrow Transplant Volume: 49 Pages: 355-60
  • DOI: 10.1038/bmt.2013.180
  • Peer Reviewed
• [Journal Article] Leukemic evolution of donor-derived cells harboring IDH2 and DNMT3A mutations after allogeneic stem cell transplantation (2014)
  • Author(s): Yasuda T, Ueno T, Fukumura K, Yamato A, Ando M, Yamaguchi H, Soda M, Kawazu M, Sai E, Yamashita Y, Murata M, Kiyoi H, Naoe T, Mano H
  • Journal Title: Leukemia Volume: 28 Pages: 426-8
  • DOI: 10.1038/leu.2013.278
  • Peer Reviewed
• [Journal Article] Risk factors and organ involvement of chronic graft-versus-host disease in Japan (2014)
  • Author(s): Kanda J, Nakasone H, Atsuta Y, Toubai T, Yokoyama H, Fukuda T, Taniguchi S, Ohashi K, Ogawa H, Eto T, Miyamura K, Morishima Y, Nagamura-Inoue T, Sakamaki H, Murata M
  • Journal Title: Bone Marrow Transplant Volume: 49 Pages: 228-35
  • DOI: 10.1038/bmt.2013.151
  • Peer Reviewed
• [Journal Article] Clinical factors predicting the response of acute graft-versus-host disease to corticosteroid therapy : an analysis from the GVHD working group of the Japan Society for Hematopoietic Cell Transplantation (2013)
  • Author(s): Murata M, Nakasone H, Kanda J, Nakane T, Furukawa T, Fukuda T, Mori T, Taniguchi S, Eto T, Ohashi K, Hino M, Inoue M, Ogawa H, Atsuta Y, Nagamura-Inoue T, Yabe H, Morishima Y, Sakamaki H, Suzuki R
  • Journal Title: Biol Blood Marrow Transplant Volume: 19 Pages: 1183-9
  • DOI: 10.1016/j.bbmt.2013.05.003
  • Peer Reviewed
• [Journal Article] Identification of a novel HLA-A*24:02-restricted adenovirus serotype 11-specific CD8^+ T-cell epitope for adoptive immunotherapy (2013)
  • Author(s): Imahashi N, Nishida T, Ito Y, Kawada J, Nakazawa Y, Toji S, Suzuki S, Terakura S, Kato T, Murata M, Naoe T
  • Journal Title: Mol Immunol Volume: 56 Pages: 399-405
  • DOI: 10.1016/j.molimm.2013.05.232
  • Peer Reviewed
• [Journal Article] Impact of hepatitis C virus infection on clinical outcome in recipients after allogeneic hematopoietic cell transplantation (2013)
  • Author(s): Nakasone H, Kurosawa S, Yakushijin K, Taniguchi S, Murata M, Ikegame K, Kobayashi T, Eto T, Miyamura K, Sakamaki H, Morishima Y, Nagamura T, Suzuki R, Fukuda T
  • Journal Title: Am J Hematol Volume: 88 Pages: 477-84
  • DOI: 10.1002/ajh.23436
  • Peer Reviewed
• [Journal Article] A case-control study of bronchiolitis obliterans syndrome following allogeneic hematopoietic stem cell transplantation (2013)
  • Author(s): Nakasone H, Kanda J, Yano S, Atsuta Y, Ago H, Fukuda T, Kakihana K, Adachi T, Yujiri T, Taniguchi S, Taguchi J, Morishima Y, Nagamura T, Sakamaki H, Mori T, Murata M
  • Journal Title: Transpl Int Volume: 26 Pages: 631-9
  • DOI: 10.1111/tri.12093
  • Peer Reviewed
• [Journal Article] Escape of leukemia blasts from HLA-specific CTL pressure in a recipient of HLA one locus-mismatched bone marrow transplantation, (equal contribution) (2012)
  • Author(s): Kato T, Terakura S, Murata M, Sugimoto K, Murase M, Iriyama C, Tomita A, Abe A, Suzuki M, Nishida T, Naoe T
  • Journal Title: Cell Immunol Volume: 276 Pages: 75-82
  • DOI: 10.1016/j.cellimm.2012.03.011
  • Peer Reviewed
• [Journal Article] Phase II study of dose-modified busulfan by real-time targeting in allogeneic hematopoietic stem cell transplantation for myeloid malignancy (2012)
  • Author(s): Kuwatsuka Y, Kohno A, Terakura S, Saito S, Shimada K, Yasuda T, Inamoto Y, Miyamura K, Sawa M, Murata M, Karasuno T, Taniguchi S, Nagafuji K, Atsuta Y, Suzuki R, Fukumoto M, Naoe T, Morishita Y
  • Journal Title: Cancer Sci Volume: 103 Pages: 1688-94
  • DOI: 10.1111/j.1349-7006.2012.02342.x
  • Peer Reviewed
• [Journal Article] Dexamethasone palmitate successfully attenuates hemophagocytic syndrome after allogeneic stem cell transplantation : macrophage-targeted steroid therapy (2012)
  • Author(s): Nishiwaki S, Nakayama T, Murata M, Nishida T, Sugimoto K, Saito S, Kato T, Mizuno H, Imahashi N, Seto A, Ozawa Y, Goto T, Koyama D, Yokohata E, Kubota N, Kamoshita S, Miyamura K, Matsumoto K, Ito M, Naoe T
  • Journal Title: Int J Hematol Volume: 95 Pages: 428-33
  • DOI: 10.1007/s12185-012-1023-z
  • Peer Reviewed
• [Journal Article] A prospective dose-finding trial using a modified continual reassessment method for optimization of fludarabine plus melphalan conditioning for marrow transplantation from unrelated donors in patients with hematopoietic malignancies (2011)
  • Author(s): Terakura S, Atsuta Y, Sawa M, Ohashi H, Kato T, Nishiwaki S, Imahashi N, Yasuda T, Murata M, Miyamura K, Suzuki R, Naoe T, Ito T, Morishita Y
  • Journal Title: Ann Oncol Volume: 22 Pages: 1865-75
  • DOI: 10.1093/annonc/mdq673
  • Peer Reviewed
• [Journal Article] Feasibility of reduced-intensity cord blood transplantation as salvage therapy for graft failure : results of a nationwide survey of 80 adult patients (2011)
  • Author(s): Waki F, Masuoka K, Fukuda T, Kanda Y, Nakamae M, Yakushijin K, Togami K, Nishiwaki K, Ueda Y, Kawano F, Kasai M, Nagafuji K, Hagihara M, Hatanaka K, Taniwaki M, Maeda Y, Shirafuji N, Mori T, Utsunomiya A, Eto T, Nakagawa H, Murata M, Uchida T, Iida H, Yakushiji K, Yamashita T, Wake A, Takahashi S, Takaue Y, Taniguchi S
  • Journal Title: Biol Blood Marrow Transplant Volume: 17 Pages: 841-51
  • DOI: 10.1016/j.bbmt.2010.09.005
  • Peer Reviewed
• [Presentation] 原発性骨髄線維症に対する幹細胞別の移植成績:JSHCTからの報告 (2014)
  • Author(s): 村田誠、西田徹也、谷口修一、大橋一輝、小川啓恭、福田隆浩、森毅彦、小林光、中世古知昭、山形昇、森島泰雄、長村登紀子、坂巻壽、熱田由子、鈴木律朗、直江知樹
  • Organizer: 第36回日本造血細胞移植学会総会
  • Place of Presentation: 沖縄コンベンションセンター、宜野湾市
  • Year and Date: 20140307-09
• [Presentation] Transplantation for primary myelofibrosis using bone marrow, peripheral blood and umbilical cord blood : a retrospective analysis of the Japan Society for Hematopoietic Cell Transplantation (2013)
  • Author(s): Murata M, Nishida T, Taniguchi S, Ohashi K, Ogawa H, Fukuda T, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Suzuki R, Naoe T
  • Organizer: The 39th Annual Meeting of the European Group for Blood and Marrow Transplantation
  • Place of Presentation: in London
  • Year and Date: 20130407-10
• [Presentation] 慢性GVHDのマネジメント (2013)
  • Author(s): 村田誠
  • Organizer: 第35回日本造血細胞移植学会総会
  • Place of Presentation: 石川県立音楽堂、金沢市, (教育講演)
  • Year and Date: 20130307-09
• [Presentation] Clinical factors predicting the response of acute graft-versus- host disease to corticosteroid therapy (2012)
  • Author(s): Murata M, Nakasone H, Kanda J, Nakane T, Furukawa T, Fukuda T, Taniguchi S, Mori T, Eto T, Morishima Y, Nagamura-Inoue T, Yabe H, Atsuta Y, Sakamaki H, Suzuki R
  • Organizer: The 54th Annual Meeting of the American Society of Hematology
  • Place of Presentation: in Atlanta, USA
  • Year and Date: 20121208-11
• [Presentation] Outcome of transplantation for primary myelofibrosis : A retrospective study of the JSHCT (2012)
  • Author(s): Murata M, Nishida T, Taniguchi S, Ohashi K, Ogawa H, Fukuda T, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Suzuki R, Naoe T
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会議場、京都市
  • Year and Date: 20121019-21
• [Presentation] 日本の急性GVHD治療の現状 (2012)
  • Author(s): 村田誠
  • Organizer: 第74回日本血液学会学術集会, (シンポジウム)
  • Place of Presentation: 京都国際会議場、京都市
  • Year and Date: 20121019-21
• [Presentation] Leukaemia escape from HLA-specific T-lymphocyte pressure in a recipient of HLA one locus-mismatched BMT (2012)
  • Author(s): Murata M, Kato T, Terakura S, Sugimoto K, Nishida T, Naoe T
  • Organizer: The 38th Annual Meeting of the European Group for Blood and Marrow Transplantation, (Best Science Poster Award)
  • Place of Presentation: in Geneva, Switzerland
  • Year and Date: 20120401-04
• [Presentation] Grade II以上の急性GVHDに対する治療成績:TRUMPデータを用いた解析 (2012)
  • Author(s): 村田誠、仲宗根秀樹、諫田淳也、中根孝彦、古川達雄、福田隆浩、谷口修一、森毅彦、衛藤徹也、森島泰雄、長村登紀子、矢部普正、熱田由子、鈴木律朗、坂巻壽
  • Organizer: 第34回日本造血細胞移植学会総会
  • Place of Presentation: グランキューブ大阪、大阪市
  • Year and Date: 20120224-25
• [Book] 急性GVHDの一次治療.みんなに役立つGVHDの基礎と臨床編集 (2013)
  • Author(s): 村田誠, (豊嶋崇徳)
  • Total Pages: 216-226
  • Publisher: 医薬ジャーナル社, (東京)
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/naika/outline/ketsueki-syuyou.html