| 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 |
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| Research Field |
Pediatrics
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| Research Institution | Shinshu University |
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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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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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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 / 免疫細胞療法 / 遺伝子改変T細胞療法 / CD19抗原 |
|---|
| 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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