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)
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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.
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