Development of a novel hematopoietic stem cell transplantation using T-cell receptor gene transduction into hematopoietic stem cells

• Project/Area Number: 26461450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Ehime University
• Principal Investigator: Taichi Azuma 愛媛大学, 医学部附属病院, 講師 (10396252)
• Co-Investigator(Renkei-kenkyūsha): Yasukawa Masaki 愛媛大学, 大学院医学系研究科, 教授 (60127917)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 白血病 / がん免疫療法 / T細胞レセプター / 遺伝子治療 / 細胞免疫療法 / WT1 / 造血幹細胞移植 / 細胞傷害性T細胞 / ヒト化マウス / 造血器腫瘍

Outline of Final Research Achievements

We performed the series of experiment in order to establish the novel hematopoietic stem cell transplantation independent on graft-versus-host disease (GVHD) using transduction of HLA-A24-restricted WT1-specific T-cell receptor (TCR) gene into hematopoietic stem cells. Human hematopoietic stem cells were transduced with HLA-A24-restricted and WT1-specific TCR gene and they were transplanted in HLA-A24-transgenic mice. WT1-specific and HLA-A24-restricted human cytotoxic T lymphocytes (CTL) were detected in humanized mice. These CTL exerted HLA-A24-restricted cytotoxicity against human leukemia cells. Our study shows the feasibility of a novel hematopoietic stem cell transplantation using transduction of cancer-specific TCR gene into hematopoietic stem cells.

Research Products

• [Journal Article] エクリズマブを使用した発作性夜間血色素尿症の一例 (2016)
  • Author(s): 玉置 南、東 太地、他
  • Journal Title: 愛媛県臨床検査技師会誌 Volume: 35 Pages: 51-55
  • Peer Reviewed
• [Journal Article] 血管内リンパ腫との鑑別が困難であった重症熱性血小板減少症候群 (2015)
  • Author(s): 東 太地、他
  • Journal Title: 臨床血液 Volume: 56 Pages: 491-495
  • NAID: 130005076023
  • Peer Reviewed
• [Presentation] Dasatinib combined with IFN-α induces a major molecular response in a patient with T315I-CML (2016)
  • Author(s): Azuma T, Tanimoto K, Asai H, Takeuchi K, Yamanouchi J, Fujiwara H, Hato T, Yasukawa M.
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜, 横浜市
  • Year and Date: 2016-10-13
• [Presentation] Clinicopathological analysis of 19 cases of MTX associated LPDs in rheumatoid arthritis (2016)
  • Author(s): Asai H, Takeuchi K, Tanimoto K, Yamanouchi J, Azuma T, Fujiwara H, Yakushijin Y, Hato T, Yasukawa M.
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜, 横浜市
  • Year and Date: 2016-10-13
• [Presentation] 治療抵抗性急性骨髄性白血病に対するAurora Kinaseペプチドワクチン療法 (2016)
  • Author(s): 谷本 一史, 藤原 弘, 越智 俊元, 東 太地, 竹内 一人, 葛島 清隆, 安川 正貴
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: パシフィコ横浜, 横浜市
  • Year and Date: 2016-10-06
• [Presentation] Adoptive immunotherapy using WT1-specific TCR gene-modified T cells for a patient with acute myeloid leukemia (2015)
  • Author(s): K Tanimoto, T Azuma, et al.
  • Organizer: The 8th International Conference on WT1 in Human Neoplasia
  • Place of Presentation: KBS Kyoto Hall（Kyoto, Japan）
  • Year and Date: 2015-11-19
  • Int'l Joint Research
• [Presentation] Effect of calreticulin mutation on the integrin αIIbβ3 function (2015)
  • Author(s): J Yamanouchi, T azuma, et al.
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県立音楽堂（石川県金沢市）
  • Year and Date: 2015-10-16