| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
TRAIL is known to cause apoptosis of hyperproliferative keratinocytes and inhibit the effector function of activated lymphocytes. Since many skin diseases have these features, we developed a method of targeting TRAIL to the epidermis. Px44 is an anti-desmoglein (Dsg) non-pathogenic antibody (Ab) previously cloned from a pemphigus patient. We linked Px44 to TRAIL to produce Px44TRAIL fusion protein. PX44TRAIL inhibit IFN-g production of activated CD4+ T cells. When targeted to proliferating (in low Ca) cultured human keratinocytes, Px44TRAIL caused apoptosis of up to 50% of cells at 16 hrs, but did not cause apoptosis of differentiating (in high Ca) keratinocytes. Furthermore, soluble Dsg3 blocked the binding and pro-apoptotic activity of Px44TRAIL. AM3-13TRAIL (in which AM3-13 is an irrelevant Ab) was negative in these assays. These data show the feasibility of targeting TRAIL to skin lesions, and suggest such therapy may be useful for hyperproliferative and inflamed skin lesions.
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