Molecular analysis of mutated isocitrate dehydrogenase and its clinical application

• Project/Area Number: 25462242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Tohoku University
• Principal Investigator: Kato Yukinari 東北大学, 医学(系)研究科(研究院), 教授 (00571811)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: IDH / IDH1-R132H / glioma / モノクローナル抗体 / HMba-2 / HMab-2 / イソクエン酸デヒドロゲナーゼ / IDH1/2 / multi-specific mAb / MsMab-1 / 診断マーカー / 免疫組織染色

Outline of Final Research Achievements

Isocitrate dehydrogenase 1/2 (IDH1/2) mutations have been reported in gliomas, and are remarkably specific to a single codon in the conserved and functionally important arginine 132 residue (R132) of IDH1 or arginine 172 residue (R172) of IDH2. To date, we have established several monoclonal antibodies (mAbs) specific for IDH1/2 mutations. Here, we established MsMab-1 mAb that reacts with IDH1-R132H, IDH1-R132S, IDH1-R132G, and IDH2-R172M, but not with wild type IDH1/2. MsMab-1 stained the IDH1-R132S or IDH1-R132G -expressing glioma cells in immunohistochemistry. MsMab-1 is expected to be useful for immunohistochemical determination of IDH1/2 mutation-bearing tumors.

Research Products

• [Journal Article] A high-sensitive HMab-2 specifically detects IDH1-R132H, the most common IDH mutation in gliomas (2015)
  • Author(s): Fujii Y, Ogasawara S, Oki H, Liu X, Kaneko MK, Takano S, Kato Y
  • Journal Title: Biochem Biophys Res Commun. Volume: 466 Issue: 4 Pages: 733-739
  • DOI: 10.1016/j.bbrc.2015.09.070
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas. (2015)
  • Author(s): Kato Y
  • Journal Title: Brain Tumor Pathol. Volume: 32 Issue: 1 Pages: 3-11
  • DOI: 10.1007/s10014-014-0202-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A novel monoclonal antibody SMab-2 recognizes endogenous IDH2-R172S of chondrosarcoma (2015)
  • Author(s): Liu X, Ogasawara S, Kaneko MK, Oki H, Hozumi Y, Goto K, Takagi M, Kato Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 459 Issue: 4 Pages: 636-642
  • DOI: 10.1016/j.bbrc.2015.02.162
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evaluation of IDH1 status in diffusely infiltrating gliomas by immunohistochemistry using anti-mutant and wild type IDH1 antibodies (2015)
  • Author(s): Ikota H, Nobusawa S, Arai H, Kato Y, Ishizawa K, Hirose T, Yokoo H.
  • Journal Title: Brain Tumor Pathol. Volume: 32 Issue: 4 Pages: 237-244
  • DOI: 10.1007/s10014-015-0222-8
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Diagnostic advantage of double immunohistochemistry using two mutation-specific anti-IDH antibodies (HMab-1 and MsMab-1) in gliomas. (2015)
  • Author(s): Takano S, Kato Y, Yamamoto T, Liu X, Ishikawa E, Kaneko MK, Ogasawara S, Matsuda M, Noguchi M, Matsumura A.
  • Journal Title: Brain Tumor Pathol. Volume: 32 Issue: 3 Pages: 169-175
  • DOI: 10.1007/s10014-015-0214-8
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Establishment of a Multi-Specific Monoclonal Antibody MsMab-1 Recognizing Both IDH1 and IDH2 Mutations (2013)
  • Author(s): Kaneko MK, Ogasawara S, Kato Y.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 230 Issue: 2 Pages: 103-109
  • DOI: 10.1620/tjem.230.103
  • NAID: 10031182999
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Isocitrate dehydrogenase 2 mutation is a frequent event in osteosarcoma detected by a multi-specific monoclonal antibody MsMab-1 (2013)
  • Author(s): Liu X, Kato Y, Kaneko MK, Sugawara M, Ogasawara S, Tsujimoto Y, Naganuma Y, Yamakawa M, Tsuchiya T, Takagi M
  • Journal Title: Cancer Med Volume: 2 Issue: 6 Pages: 803-814
  • DOI: 10.1002/cam4.149
  • Peer Reviewed
• [Journal Article] Multi-specific monoclonal antibody MsMab-2 recognizes IDH1-R132L and IDH2-R172M mutations. (2013)
  • Author(s): Ogasawara S, Kaneko MK, Tsujimoto Y, Liu X, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 32 Issue: 6 Pages: 377-381
  • DOI: 10.1089/mab.2013.0050
  • Peer Reviewed
• [Journal Article] Novel monoclonal antibodies GMab-r1 and LMab-1 specifically recognize IDH1-R132G and IDH1-R132L mutations. (2013)
  • Author(s): Kaneko MK, Tsujimoto Y, Hozumi Y, Goto K, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 32(3) Issue: 3 Pages: 224-228
  • DOI: 10.1089/mab.2013.0006
  • Peer Reviewed
• [Journal Article] Generation of a novel monoclonalantibody WMab-1 specific forIDH2-R172W mutation (2013)
  • Author(s): Kato Y, KanekoMK
  • Journal Title: Biochem Biophys Res Commun Volume: 19;433(4) Issue: 4 Pages: 374-8
  • DOI: 10.1016/j.bbrc.2013.02.106
  • Peer Reviewed
• [Journal Article] A novel monoclonal antibody GMab-m1 specifically recognizes IDH1-R132G mutation. (2013)
  • Author(s): Kato Y, Natsume A, Kaneko MK.
  • Journal Title: Biochem Biophys Res Commun. Volume: 432 Issue: 4 Pages: 564-567
  • DOI: 10.1016/j.bbrc.2013.02.049
  • Peer Reviewed
• [Journal Article] Establishment of novel monoclonalantibodies KMab-1 and MMab-1 specificfor IDH2 mutations (2013)
  • Author(s): Kaneko MK, MoritaS, Tsujimoto Y, Yanagiya R, Nasu K,Sasaki H, Hozumi Y, Goto K, Natsume A,Watanabe M, Kumabe T, Takano S, KatoY
  • Journal Title: Biochem Biophys Res Commun Volume: 1;432(1) Issue: 1 Pages: 40-5
  • DOI: 10.1016/j.bbrc.2013.01.088
  • Peer Reviewed
• [Journal Article] Progressive adult primary glioblastoma in the medulla oblongata with an unmethylated MGMT promoter and without an IDH mutation (2012)
  • Author(s): Yoshikawa A, Nakada M, Watanabe T, Hayashi Y, Sabit H, Kato Y, Suzuki S, Ooi A, Sato H, Hamada JI
  • Journal Title: Brain Tumor Pathol Volume: (in press) Issue: 3 Pages: 28-28
  • DOI: 10.1007/s10014-012-0118-9
  • Peer Reviewed
• [Presentation] 変異型IDHに対する特異的抗体の開発 (2015)
  • Author(s): 加藤幸成
  • Organizer: 第74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）
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] 新規IDH2抗体による軟骨肉腫におけるIDH2-R172S変異の解析 (2015)
  • Author(s): 劉 興、小笠原諭、金子美華、大木弘治、加藤幸成
  • Organizer: 第74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）
  • Year and Date: 2015-10-08
• [Presentation] 変異型IDH1/2に対する新規抗体MsMab-1の樹立 (2013)
  • Author(s): 加藤幸成、小笠原諭、金子美華
  • Organizer: 第７２回日本癌学会学術総会
  • Place of Presentation: パシィフィコ横浜（横浜市）
• [Presentation] 変異型IDH1/2に対するMulti-specific抗体の作製 (2013)
  • Author(s): 加藤幸成、金子美華
  • Organizer: 第一回がんと代謝研究会
  • Place of Presentation: 鶴岡メタボロームキャンパス レクチャーホール（鶴岡市）
• [Presentation] 骨肉腫における変異型イソクエン酸デヒドロゲナーゼの発現解析
  • Author(s): 劉興、菅原正登、金子美華、小笠原諭、辻本雄太、長沼靖、土屋登嗣、高木理彰、加藤幸成
  • Organizer: 第３３回日本分子腫瘍マーカー研究会
  • Place of Presentation: パシィフィコ横浜（横浜市）
• [Presentation] 変異型イソクエン酸デヒドロゲナーゼ１／２に対するMuti-specific抗体の作製
  • Author(s): 辻本雄太、金子美華、小笠原諭、加藤幸成
  • Organizer: 第３３回日本分子腫瘍マーカー研究会
  • Place of Presentation: パシィフィコ横浜（横浜市）
• [Remarks] 東北大学大学院医学系研究科地域イノベーション分野
  • URL: http://www.med-tohoku-antibody.com/index.htm
• [Remarks] 東北大学大学院医学系研究科・加藤研究室
  • URL: http://www.med-tohoku-antibody.com/