EFFICACY AND SAFETY OF T CELLS WITH CEA-SPECIFIC CHIMERIC ANTIGEN RECEPTOR FOR CANCER IMMUNOTHERAPY

Research Project

Project/Area Number	24591899
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	General surgery
Research Institution	Mie University
Principal Investigator	WANG Linan 三重大学, 医学(系)研究科(研究院), 特任助教(研究担当) (00589484)
Co-Investigator(Kenkyū-buntansha)	KATO Takuma 三重大学, 大学院医学系研究科, 准教授 (60224515)
Project Period (FY)	2012-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000) Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	CEA-Tgマウス / CAR-T細胞 / キメラ抗原受容体 / 胎児性癌抗原 / T細胞受容体 / GITR / がん治療 / 複刺激シグナル分子 / 癌胎児性抗原
Outline of Final Research Achievements	(1)Retrovirus vector composed of anti-CEA scFV and signaling domain of human or mouse CD3 and CD28 successfully transduced human or mouse T cells, respectively, to express functional CAR.(2) Adoptive therapy with CEA-specific CAR expressing human T cells to tumor bearing lymphopenic NOG mouse inhibited growth of CEA positive, but not CEA negative, tumor. (3) Likewise, adoptive therapy with CEA-specific CAR expressing mouse T cells to tumor bearing lymphoreplete CEA-Tg mouse inhibited growth of CEA-positive tumor only when the mouse received lymphodepleting preconditioning. (4) However, this tumor growth inhibition was associated with inflammation in lungs in a manner independent of CAR-specificity and severe weight loss in a manner dependent of CAR-specificity. (5) CEA-specific CAR-T cells induce systemic cytokine response that could induce anorexia in CEA-Tg. (6) CEA-specific CAR-T cells induce malnutrition in CEA-Tg.