Basic study of immunotherapy with peptide vaccine in PNH

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591067
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Fukushima Medical University
• Principal Investigator: NOJI Hideyoshi 福島県立医科大学, 医学部, 講師 (20347214)
• Co-Investigator(Kenkyū-buntansha): SHICHISHIMA Tsutomu 福島県立医科大学, 医学部, 研究員 (10192105)
• Co-Investigator(Renkei-kenkyūsha): FUJITA Teizo 福島県立医科大学, 医学部, 教授 (20134223) ; MANO Hiroyuki 自治医科大学, 医学部, 教授 (90240704)
• Project Period (FY): 2010 – 2012
• Keywords: 血液免疫学

Research Abstract

We planned this study in order to develop immunotherapy with peptide vaccine for paroxysmal nocturnal hemoglobinuria (PNH). 1) We investigated gene(s)associated with the expansion of PNH clones by microarray methods to clarify target for the therapy. 2) We tried to prepare a xenogeneic model of PNH resulting from the adoptive transfer of BM ACC133+cells from PNH patients into NOG mice. We have a next step such as assessment of effects for PNH clone and reactions of immune system in PNH patients by WT1 peptide vaccine.

Research Products

• [Journal Article] A Japanese case of chronic lymphocytic leukemia with t(1;6) (2012)
  • Author(s): Harada K, Ikeda K, Matsumoto H, Furukawa M, Takahashi H, Ohkawara H, Noji H, Tasaki K, Abe M, Ogawa K, Takeishi Y
  • Journal Title: Exp Hematol Oncol Volume: 1 (1) Pages: 28
  • DOI: DOI:10.1186/2162-3619-1-28
• [Journal Article] Deregulated expression of HMGA2 is implicated in clonal expansion of PIGA deficient cells in paroxysmal nocturnal haemoglobinuria (2012)
  • Author(s): Murakami Y, Inoue N, Shichishima T, Ohta R, Noji H, Maeda Y, Nishimura J, Kanakura Y, Kinoshita T, haemoglobinuria D
  • Journal Title: Br J Haematol Volume: 156 (3) Pages: 383-387
  • DOI: DOI:10.1111/j.1365-2141.2011.08914.x
• [Journal Article] Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation (2012)
  • Author(s): Ngoma A, Ikeda K, Hashimoto Y, Mochizuki K, Takahashi H, Sano H, Matsumoto H, Noji H, Saito S, Kikuta A, Ogawa K, Ohtsuka M, Abe M, Nollet K, Ohto H
  • Journal Title: Int J Hematol Volume: 95 (1) Pages: 86-94
  • DOI: DOI:10.1007/s12185-011-0976-7
• [Journal Article] Maturity-dependent fractionation of neutrophil progenitors: A new method to examine in vivo expression profiles of differentiation-regulating genes (2012)
  • Author(s): Hu H, Shikama Y, Shichishima T, Ikeda K, Akutsu K, Ono T, Kimura H, Ogawa K, Noji H, Takeishi Y, Kimura J
  • Journal Title: Exp Hematol Volume: 40 (8) Pages: 675-681
  • DOI: DOI:10.1016/j.exphem.2012.03.003
• [Journal Article] Safety and feasibility of high-dose ranimustine (MCNU), carboplatin, etoposide, and cyclophosphamide (MCVC) therapy followed by autologous stem cell transplantation for malignant lymphoma (2012)
  • Author(s): Kameoka Y, Takahashi N, Ishizawa K, Kato Y, Ito J, Sasaki O, Murai K, Noji H, Hirokawa M, Tajima K, Shichishima T, Ishida Y, Harigae H, Sawada K
  • Journal Title: Int J Hematol Volume: 96 (5) Pages: 624-630
  • DOI: DOI:10.1007/s12185-012-1186-7
• [Journal Article] T-cell prolymphocytic leukemia in Japan: is it a variant?. (2012)
  • Author(s): Kameoka J, Takahashi N, Noji H, Murai K, Tajima K, Kameoka Y, Sato S, Shichishima T, Ishida Y, Harigae H, Sawada K
  • Journal Title: Int J Hematol Volume: 96 (5) Pages: 660-667
  • DOI: DOI:10.1007/s12185-012-1077-y
• [Journal Article] Comparison of long-term clinical outcomes of CHOP chemotherapy between Japanese patients with nodal peripheral T-cell lymphomas and those with diffuse large B-cell lymphoma in the study group of the Tohoku Hematology Forum (2011)
  • Author(s): Akagi T, Takahashi N, Yamaguchi K, Ishizawa K, Murai K, Tajima K, Ikeda K, Kameoka Y, Kameoka J, Ito S, Kato Y, Noji H, Shichishima T, Itoh J, Ichinohasama R, Harigae H, Ishida Y, Sawada K
  • Journal Title: J Clin Exp Hematopathol Volume: 51 (1) Pages: 29-35
  • DOI: DOI:10.3960/jslrt.51.29
• [Journal Article] Impairment of FOS mRNA induction by a translation inhibitor puromycin in granulocytes from myelodysplastic syndrome patients. (2011)
  • Author(s): Shikama Y, XiaoMin F, Shichishima T, Ono T, Noji H, Ikeda K, Ogawa K, Takeishi Y, Kimura J
  • Journal Title: Br J Haematol Volume: 154 (4) Pages: 525-527
  • DOI: DOI:10.1111/j.1365-2141.2010.08504.x
• [Journal Article] A long-term remission of renal amyloidosis with nephrotic syndrome after autologous peripheral blood stem-cell transplantation (2010)
  • Author(s): Ogawa K, Ikeda K, Furukawa M, Harada-Shirado K, Mashimo Y, Takahashi H, Matsumoto H, Kimura S, Shichishima-Nakamura A, Ohkawara H, Hashimoto Y, Asahi K, Noji H, Ohto H, Takeishi Y
  • Journal Title: Fukushima J Med Sci Volume: 56 (2) Pages: 151-156
  • DOI: DOI:10.5387/fms.56.151
• [Journal Article] Hematopoietic stem cell transplantation in the department of hematology, Fukushima Medical University (2010)
  • Author(s): Ogawa K, Noji H, Furukawa M, Harada-Shirado K, Mashimo Y, Takahashi H, Matsumoto H, Kimura S, Shichishima-Nakamura A, Ohkawara H, Ikeda K, Ohto H, Takeishi Y
  • Journal Title: Fukushima J Med Sci Volume: 56 (2) Pages: 107-114
  • DOI: DOI:10.5387/fms.56.107
• [Journal Article] Low concentration of serum haptoglobin has impact on understanding complex pathophysiology in patients with acquired bone marrow failure syndromes (2010)
  • Author(s): Shichishima T, Ikeda K, Takahashi N, Kameoka J, Tajima K, Murai K, Tamai Y, Shichishima-Nakamura A, Akutsu K, Noji H, Okamoto M, Kimura H, Harigae H, Oyamada T, Kamesaki T, Takeishi Y, Sawada K
  • Journal Title: Int J Hematol Volume: 91(4) Pages: 602-610
  • DOI: DOI:10.1007/s12185-010-0559-z
• [Presentation] Impairment of HuR-mediated FOS mRNA stabilization in granulocytes from myelodysplastic syndrome patients (2012)
  • Author(s): Xiaomin F, Yayoi S, Shichishima T, Noji H, Ikeda K, Ogawa K, Takeishi Y, Kimura J
  • Organizer: 2012 American Society of Hematology (ASH) Annual Meeting and Exposition
  • Place of Presentation: Atlanta, Georgia, USA
  • Year and Date: 20121208-11
• [Presentation] A rare genetic polymorphism in C5 confers poor response to the anti-C5 monoclonal antibody eculizumab by nine Japanese patients with PNH. (2012)
  • Author(s): Nishimura J, Yamamoto M, Hayashi S, Ohyashiki K, Ando K, Noji H, Kitamura K, Eto T, Ando T, Masuko M, Shibayama H, Hase M, Lan L, Tamburini P, Inazawa J, Kinoshita T, Kanakura Y
  • Organizer: 2012 American Society of Hematology (ASH) Annual Meeting and Exposition
  • Place of Presentation: Atlanta, Georgia, USA
  • Year and Date: 20121208-11
• [Presentation] Morphologic and cytogenetic examinations with bone marrow cells in PNH patients. (2012)
  • Author(s): Noji H, Hamanaka S, Yamaguchi K, Ogawa K, Murai K, Kimura H, Mita M, Suzuki I, Kohno K, Kimura S, Saitoh Y, Hatta S, Michishita Y, Kanbayashi H, Ishida Y, Harigae H, Sawada K, Takeishi Y, Shichishima T
  • Organizer: 第74回 日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] Detection of PNH-type cells using high-resolution flow cytometry: Interim analysis of OPTIMA study. (2012)
  • Author(s): Hosokawa K, Sugimori C, Yamamoto M, Nishimura J, Yonemura Y, Obara N, Noji H, Nakamura Y, Ando K, Shichishima T, Ninomiya H, Chiba S, Kawaguchi T, Nakao S, Kanakura Y
  • Organizer: 第74回 日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] Mechanism of impaired FOS mRNA induction by emetine in myelodysplastic syndrome granulocytes. (2012)
  • Author(s): Feng X, Shikama Y, Noji H, Shichishima T, Ikeda K, Ogawa K, Takeishi Y, Kimura J
  • Organizer: 第74回 日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] A preliminary study on telomere length of granulocytes and mononuclear cells in PNH patients (2012)
  • Author(s): Takahashi H, Noji H, Takeishi Y, Shichishima T
  • Organizer: 第74回 日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] Erythema annulare centrifugum in a patient with paroxysmal nocturnal hemoglobinuria. (2012)
  • Author(s): Noji H, Usuki K, Otsuka M, Horiuchi H, Yamamoto T, Takahashi H, Takeishi Y, Shichishima T
  • Organizer: 第74回 日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] Paroxysmal nocturnal hemoglobinuria in a patient with del(5q)(q23q32) myelodysplastic syndromes. (2012)
  • Author(s): Mita M, Nakamura K, Takahashi H, Noji H, Takeishi Y, Shichishima T
  • Organizer: 第74回 日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] Del(13q) myelodysplastic syndromes in a patient with paroxysmal nocturnal hemoglobinuria (PNH). (2012)
  • Author(s): Kimura S, Saitou Y, Kanbayashi H, Matuda S, Odajima H, Takahashi H, Noji H, Takeishi Y, Shichishima T
  • Organizer: 第74回 日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] OPTIMA試験:高精度フローサイトメトリー法によるGPIアンカー膜蛋白欠損血球の検出. (2012)
  • Author(s): 山本正樹, 西村純一, 細川晃平, 杉盛千春, 米村雄士, 小原 直, 中村嘉彦, 野地秀義, 七島 勉, 安藤 潔, 二宮治彦, 千葉 滋, 川口辰哉, 中尾眞二, 金倉 譲
  • Organizer: 第49回 補体シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 20120824-25
• [Presentation] OPTIMA試験:高精度フローサイトメトリー法によるGPIアンカー型蛋白欠損血球の検出 (2012)
  • Author(s): 山本正樹, 西村純一, 細川晃平, 杉盛千春, 米村雄士, 小原 直, 野地秀義, 中村嘉彦, 安藤 潔, 七島 勉, 二宮治彦, 千葉 滋, 川口辰哉, 中尾眞二, 金倉 譲
  • Organizer: 第22回 サイトメトリー学会
  • Place of Presentation: 豊中
  • Year and Date: 20120629-30
• [Presentation] IRF4に関連した染色体転座T(1;6)を有した慢性リンパ性白血病の一例. (2012)
  • Author(s): 原田佳代, 池田和彦, 松本勇人, 高橋裕志, 七島晶子, 大河原浩, 野地秀義, 田崎和洋, 小川一英, 阿部正文, 竹石恭知
  • Organizer: 第52回 日本リンパ網内系学会総会
  • Place of Presentation: 福島
  • Year and Date: 20120614-16
• [Presentation] 特別講演:PNHの病態と治療戦略について (2012)
  • Author(s): 野地秀義
  • Organizer: 函館PNHセミナー
  • Place of Presentation: 函館
  • Year and Date: 2012-10-05
• [Presentation] Paroxysmal nocturnal hemoglobinuria (PNH)症例におけるEculizumab治療の赤血球結合IgGおよびC3に対する影響 (2012)
  • Author(s): 野地秀義, 亀崎豊実, 濱中純子, 山口公平, 神林裕行, 竹石恭知, 七島 勉, 東北PNH研究会
  • Organizer: 第4回 造血器腫瘍免疫療法研究会
  • Place of Presentation: 金沢
  • Year and Date: 2012-08-18
• [Presentation] 骨髄低形成を伴うPNH症例に対するEculizmab使用経験 (2012)
  • Author(s): 野地秀義, 七島 勉, 竹石恭知
  • Organizer: 2012 Japan PNH Masters
  • Place of Presentation: 東京
  • Year and Date: 2012-07-28
• [Presentation] 講 演:OPTIMAの概要と進捗 (2012)
  • Author(s): 野地秀義
  • Organizer: 北海道PNH研究会
  • Place of Presentation: 札幌
  • Year and Date: 2012-01-20
• [Presentation] Phasell Study of Dasatinib safety and efficacy for CP-CML at Tohoku. (2011)
  • Author(s): Akagi T, Murai K, Shimosegawa K, Ishizawa K, Sugawara T, Yokoyama H, Noji H, Ogawa K, Tajima K, Miyashita Y, Ooba K, Sakamoto J, Kubo K, Harigae H, Ishida Y
  • Organizer: 第73回 日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111014-16
• [Presentation] PNH-type cells by flow cytometric methods with a monoclonal antibody and FLAER in BMFS patients. (2011)
  • Author(s): Takahashi H, Shichishima T, Noji H, Ogawa K, Takeishi Y
  • Organizer: 第73回 日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111014-16
• [Presentation] 補体研究:基礎から臨床へ:発作性夜間血色素尿症をはじめとするGPI欠損症について. (2011)
  • Author(s): 村上良子, 井上徳光, 七島 勉, 太田里永子, 野地秀義, 前田裕輔, 西村純一, 木下タロウ
  • Organizer: 第48回 補体シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 20110902-03
• [Presentation] Paroxysmal nocturnal hemoglobinuria (PNH) 8症例におけるEculizumabの効果および安全性. (2011)
  • Author(s): 野地秀義, 七島 勉, 高橋裕志, 小川一英, 竹石恭知
  • Organizer: 第3回 造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 別府
  • Year and Date: 20110820-21
• [Presentation] 自家末梢血幹細胞移植後にサイトメガロウイルス感染が原因と考えられた血球貪食症候群の2 例(Cytomegalo virus caused hemophagocytic syndrom after autologous peripheral blood stem cell transplantation). (2011)
  • Author(s): 松本勇人, 古川未希, 原田佳代, 真下由美子, 高橋裕志, 木村 哲, 七島晶子, 大河原浩, 野地秀義, 小川一英, 大戸斉, 竹石恭知
  • Organizer: 第33回 日本造血細胞移植学会総会
  • Place of Presentation: 松山
  • Year and Date: 20110309-10
• [Presentation] デフェラシロクス長期投与後に著明に造血能が改善した重症型再生不良性貧血の一例. (2011)
  • Author(s): 野地秀義
  • Organizer: Iron Overload Case Study Forum 2011
  • Place of Presentation: 東京
  • Year and Date: 2011-08-27
• [Presentation] Expression of HMGA2 in blood cells from patients with paroxysmal nocturnal hemoglobinuria. (2010)
  • Author(s): Murakami Y, Inoue N, Shichishima T, Noji H, Nishimura J, Kanakura Y, Kinoshita T
  • Organizer: 52nd American Society of Hematology (ASH) Annual Meeting and Exposition
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 20101204-07
• [Presentation] 急性骨髄性白血病(AML)症例におけるCD59陰性白血病細胞の出現Appearance of CD59-negative leukemic cells in patients with acute myeloid leukemia. (2010)
  • Author(s): 野地秀義, 七島 勉, 岡本正俊, 池田和彦, 七島晶子, 阿久津和子, 竹石恭知
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] 後天性骨髄不全症候群(BMFS)症例におけるFLAERによるGPIアンカー発現の検討Studies on GPI-anchor expressions by flow cytometry using FLAER in patients with acquired BMFS. (2010)
  • Author(s): 高橋裕志, 七島 勉, 野地秀義, 古川未希, 七島晶子, 竹石恭知
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Safety, feasibility and efficacy of MCVC therapy followed by auto-PBSCT for malignant lymphoma. (2010)
  • Author(s): Kameoka Y, Takahashi N, Hirokawa M, Aoki Y, Yamamoto J, Kato Y, Hiroshima Y, Ito J, Noji H, Ishizawa K, Shichishima T, Ishida Y, Harigae H, Sawada K
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Impaired c-fos induction by emetin in granulocytes from myelodysplastic syndrome patients. (2010)
  • Author(s): Feng X, Shikama Y, Shichishima T, Noji H, Ogawa K, Takeishi Y
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] 血液学的およびクローン性寛解に至った発作性夜間ヘモグロビン尿症の2症例Two paroxysmal nocturnal hemoglobinuria patients reached hematological and clonal remission. (2010)
  • Author(s): 古川未希, 野地秀義, 七島 勉, 原田佳代, 眞下由美子, 高橋裕志, 松本勇人, 木村 哲, 七島晶子, 大河原浩, 小川一英, 竹石恭知
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Clinical and biological features of T-cell prolymphocytic leukemia in Japan. (2010)
  • Author(s): Kameoka J, Takahashi N, Noji H, Murai K, Tajima K, Kameoka Y, Shichishima T, Ishida Y, Harigae H, Sawada K
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Analysis of autologous PBSCT in four patients with cardiac amyloidosis. (2010)
  • Author(s): Ogawa K, Kimura S, Furukawa M, Harada K, Mashimo Y, Takahashi H, Matsumoto H, Shichishima-Nakamura A, Ohkawara H, Noji H, Shichishima T, Ohto H, Takeishi Y
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] 急性骨髄性白血病へ移行した骨髄異形成症候群を合併した発作性夜間ヘモグロビン尿症の一例A PNH patient complained of MDS and developed AML. (2010)
  • Author(s): 木村 哲, 野地秀義, 七島 勉, 大河原浩, 古川未希, 原田佳代, 眞下由美子, 高橋裕志, 松本勇人, 七島晶子, 小川一英, 竹石恭知
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] 発作性夜間ヘモグロビン尿症4症例におけるヒト化モノクローナル抗C5抗体 (Eculizumab) の効果および安全性の検討. (2010)
  • Author(s): 野地秀義, 七島 勉, 高橋裕志, 小川一英, 竹石恭知
  • Organizer: 第47回 補体シンポジウム
  • Place of Presentation: 福島
  • Year and Date: 20100910-11
• [Presentation] 発作性夜間ヘモグロビン尿症(PNH)4症例におけるEculizumabの効果および安全性. (2010)
  • Author(s): 野地秀義, 七島 勉, 高橋裕志, 小川一英, 竹石恭知
  • Organizer: 第2回 造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 松山
  • Year and Date: 20100828-29