Gene-modified T cell therapy for refractory acute myeloid leukemia harboring a FLT3/ITD mutation

• Project/Area Number: 26461574
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: NAKAZAWA Yozo 信州大学, 学術研究院医学系, 教授 (60397312)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: キメラ抗原受容体 / T細胞療法 / がん免疫療法 / 急性骨髄性白血病 / CAR-T療法 / Flt3/ITD / Flt3 / FLT3/ITD

Outline of Final Research Achievements

Patients with FLT3/ITD-mutated acute myeloid leukemia (AML) have a poor prognosis. A FLT3/ITD-mutated AML cell line, MV4-11, highly express GM-CSF receptors (GMR). We developed T cells engineered to express a chimeric antigen receptor (CAR) targeting the GMR. GMR CAR T cells eliminated MV4-11 cells up to 98% after a 5 days-coculture at a T cells: leukemia cells ratio of 1:5. Adoptive immunotherapy using GMR CAR T cells may a promising option for AML harboring a FLT3/ITD mutation.

Research Products

• [Int'l Joint Research] Baylor College of Medicine/Vanderbilt University(米国)
• [Journal Article] Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34(+) cells of juvenile myelomonocytic leukemia (2016)
  • Author(s): Nakazawa Y, Matsuda K, Kurata T, Sueki A, Tanaka M, Sakashita K, Imai C, Wilson MH, Koike K
  • Journal Title: J Hematol Oncol Volume: 9 Issue: 1 Pages: 27-27
  • DOI: 10.1186/s13045-016-0256-3
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 小児血液腫瘍に対するキメラ抗原受容体を用いた遺伝子改変T細胞療法の開発 (2016)
  • Author(s): 中沢洋三
  • Journal Title: 臨床血液 Volume: 印刷中
  • Peer Reviewed
• [Journal Article] キメラ抗原受容体(CAR)遺伝子改変T細胞療法 (2015)
  • Author(s): 中沢洋三
  • Journal Title: がん分子標的治療 Volume: 13 Pages: 59-65
• [Journal Article] Anti-leukemic potency of piggyBac-mediated CD19-specific T cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. (2014)
  • Author(s): Saito S, Nakazawa Y, Sueki A, Matsuda K, Tanaka M, Yanagisawa R, Maeda Y, Sato Y, Okabe S, Inukai T, Sugita K, Wilson MH, Rooney CM, Koike K.
  • Journal Title: Cytotherapy Volume: 16 Issue: 9 Pages: 1257-1269
  • DOI: 10.1016/j.jcyt.2014.05.022
  • Peer Reviewed / Open Access
• [Presentation] Development of T cells redirected to GM-CSF receptor with a ligand-based CAR for myeloid neoplasms (2016)
  • Author(s): Shigeru Nakano, Daisuke Morita, Kazuyuki Matsuda, Hideki Ohnota, Kazuhiro Hongo, Kenichi Koike, Yozo Nakazawa
  • Organizer: 日本血液学会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2016-10-13
• [Presentation] Ligand-based chimeric antigen receptor-modified T cells targeting CD116 for the treatment of acute myeloid leukemia (2016)
  • Author(s): Shigeru Nakano, Daisuke Morita, Kazuyuki Matsuda, Hideki Ohnota, Kazuhiro Hongo, Kenichi Koike, Yozo Nakazawa
  • Organizer: 日本遺伝子細胞治療学会
  • Place of Presentation: 虎ノ門ヒルズフォーラム、東京
  • Year and Date: 2016-07-28
• [Presentation] 難治性がんに対するキメラ抗原受容体を用いた遺伝子改変Ｔ細胞療法 (2015)
  • Author(s): 中沢洋三
  • Organizer: 第4回日本免疫・細胞治療学会学術集会
  • Place of Presentation: ベルサール九段（東京都千代田区）
  • Year and Date: 2015-12-05
  • Invited
• [Presentation] Gene-modified T-cell therapy using chimeric antigen receptors for childhood neoplasms (2015)
  • Author(s): 中沢洋三
  • Organizer: 第57回日本小児血液がん学会学術集会
  • Place of Presentation: 甲府富士屋ホテル（山梨県甲府市）
  • Year and Date: 2015-11-27
  • Invited
• [Presentation] Gene-modified T-cell therapy using chimeric antigen receptors．for childhood hematological malignancies (2015)
  • Author(s): 中沢洋三
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 金沢市アートホール（石川県金沢市）
  • Year and Date: 2015-10-16
  • Invited
• [Presentation] Cancer immunotherapy using chimeric antigen receptors: advances, issues, and future directions (2015)
  • Author(s): 中沢洋三
  • Organizer: 第21回日本遺伝子治療学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-07-24
  • Invited
• [Presentation] キメラ抗原受容体（CAR）を用いた遺伝子改変T細胞療法 (2014)
  • Author(s): 中沢洋三
  • Organizer: 日本がん免疫学会
  • Place of Presentation: 松山市ひめぎんホール
  • Year and Date: 2014-07-30 – 2014-08-01
  • Invited
• [Presentation] Potency of piggyBac transposon-mediated CD19-specific T-cells against drug-resistant Philadelphia chromosome-positive acute lymphoblastic leukemia (2014)
  • Author(s): Shoji Saito, Yozo Nakazawa, Miyuki Tanaka, Ryu Yanagisawa, Akane Sueki, Kazuyuki Matsuda, Matthew H. Wilson, Cliona Rooney, Kenichi Koike
  • Organizer: International Society for Cellular Thrapy
  • Place of Presentation: フランス（パリ）
  • Year and Date: 2014-04-23 – 2014-04-26
• [Book] 次世代のがん治療薬・診断のための研究開発 (2016)
  • Author(s): 中沢洋三、共著
  • Total Pages: 350
  • Publisher: 技術情報出版
• [Patent(Industrial Property Rights)] 遺伝子改変細胞及びその作製方法 (2016)
  • Inventor(s): 中沢洋三、松田和之、中野茂
  • Industrial Property Rights Holder: 信州大学、（株）キッセイ薬品工業
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-182293
  • Filing Date: 2016-09-16