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

2014 Fiscal Year Final Research Report

• 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
• Keywords: CEA-Tgマウス / CAR-T細胞

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.

Free Research Field

遺伝子免疫分子治療学