PiggyBac transposon-mediated CD19-specific T cells against Ph+ acute lymphoblastic leukemia

2013 Fiscal Year Final Research Report

• Project/Area Number: 24791050
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: SAITO Shoji 信州大学, 医学部附属病院, 助教 (10623762)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: がん / 細胞免疫療法 / キメラ抗原受容体 / 急性リンパ性白血病 / チロシンキナーゼ阻害薬 / フィラデルフィア染色体

Research Abstract

To develop an alternative treatment for Ph+ALL resistant to tyrosine kinase inhibitors (TKIs), we evaluated anti-Ph+ALL activity of T-cells nonvirally engineered to express a chimeric antigen receptor (CAR) targeting CD19. A CD19-CAR gene was delivered into mononuclear cells from healthy donors using piggyBac transposons and 4D-Nucleofector System. We successfully generated an adequate number of CAR-T cells from 10-ml blood using piggyBac transposons, 4D-Nulclofector, and serum-free, tumor cell/virus-free culture method to reduce a potential risk and facilitate cGMP approval. CAR-T cells exhibited marked cytotoxicity against Ph+ALL regardless of TKI-resistance and subsequent proliferation by autocrine IL-2 secretion. Our CD19-specific T-cell therapy may be an effective and safe option for relapsed/refractory Ph+ALL.

Research Products

• [Journal Article] Anti-leukemic potency of piggyBac-mediated CD19-specificT cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (2014)
  • Author(s): Shoji Saito, Yozo Nakazawa, Miyuki Tanaka, Ryu Yanagisawa, Akane Sueki, Kazuyuki Matsuda, Yasuhiro Maeda, Yuko Sato, Seiichi Okabe, Takeshi Inukai, Kanji Sugita, Matthew H. Wilson, Cliona M. Rooney, and Kenichi Koike
  • Journal Title: Cytotherapy Volume: (in press)
  • Peer Reviewed
• [Presentation] 薬剤耐性Ph陽性急性リンパ性白血病に対するpiggyBacトランスポゾン遺伝子改変CD19特異的T細胞療法の開発 (2012)
  • Author(s): 齋藤章治, 中沢洋三, 田中美幸, 柳沢龍, 松田和之, 前田裕弘, 犬飼岳史, 杉田完爾, 小池健一
  • Organizer: 小児血液がん学会
  • Place of Presentation: 横浜市
  • Year and Date: 2012-12-01
• [Presentation] CD19-specific T-cell therapy for Ph+ALL using piggyBac transposon-based gene modification (2012)
  • Author(s): Shoji Saito, Yozo Nakazawa, Miyuki Tanaka, Ryu Yanagisawa, Kazuyuki Matsuda, Yasuhiro Maeda, Takeshi Inukai, Kanji Sugita, Kenichi Koike
  • Organizer: 日本血液学会
  • Place of Presentation: 京都市
  • Year and Date: 2012-10-20
• [Presentation] CD19-specific T-cell therapy for refractory Philadelphia-chromosome-positive acute lymphoblastic leukemia using PiggyBac transposon-based gene modification and low autoserum-containing, but xeno-free and tumor cell line-free culture system (2012)
  • Author(s): Shoji Saito, Yozo Nakazawa, Miyuki Tanaka, Ryu Yanagisawa, Yasuhiro Maeda, Takeshi Inukai, Kanji Sugita, Matthew H Wilson, Cliona M Rooney, and Kenichi Koike
  • Organizer: Annual Meetings of American Society of Gene Therapy
  • Place of Presentation: Philadelphia PA
  • Year and Date: 2012-05-18
• [Presentation] 難治性急性リンパ性白血病に対するCD19特異的遺伝子改変T細胞療法の開発 (2012)
  • Author(s): 齋藤章治, 中沢洋三, 平林耕一, 松田和之, 杉田完爾, 小池健一
  • Organizer: 日本小児科学会
  • Place of Presentation: 福岡市
  • Year and Date: 2012-04-21