| Project/Area Number |
25670553
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | Mie University |
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Principal Investigator |
KATO Takuma 三重大学, 医学(系)研究科(研究院), 准教授 (60224515)
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| Co-Investigator(Kenkyū-buntansha) |
WANG Linan 三重大学, 大学院医学系研究科, 特任助教(研究担当) (00589484)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | キメラ抗原受容体 / T細胞輸注療法 / 癌胎児性抗原 |
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| Outline of Final Research Achievements |
CEA is cell surface antigens highly expressed on various cancer cell types but also expressed on healthy tissues, thus its feasibility as a target for CAR-modified T cell therapy will be required to augment efficacy, but also awaited before establishing its safety in terms of on-target-off-tumor effects. In the present study, we sought to determine whether CAR-CD4 T cells act in concert with CAR-CD8 T cells to exert anti-tumor activity in vivo using CEA-transgenic mouse expressing CEA as a self-antigen. The adoptive transfer of CEA specific CAR expression CD4 T cells did not enhance the efficacy of CEA-specific CAR-expressing CD8 T cells to exert anti-tumor activity. The adoptive transfer in conjunction with lymphodepleting preconditioning mediated significant tumor regression but caused weight loss in CEA-Tg mice. This weight loss was not associated with overt inflammation in CEA-expressing tissues, but malnutrition with elevated systemic levels of cytokines linked to anorexia.
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