2013 Fiscal Year Final Research Report
PiggyBac transposon-mediated CD19-specific T cells against Ph+ acute lymphoblastic leukemia
Project/Area Number |
24791050
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
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Research Institution | Shinshu University |
Principal Investigator |
SAITO Shoji 信州大学, 医学部附属病院, 助教 (10623762)
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Project Period (FY) |
2012-04-01 – 2014-03-31
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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.
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[Journal Article] Anti-leukemic potency of piggyBac-mediated CD19-specificT cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia2014
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
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Journal Title
Cytotherapy
Volume: (in press)
Peer Reviewed
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[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 system2012
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
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