2015 Fiscal Year Final Research Report
Development of the skin-targeted drug delivery system by using non-pathogenic pemphigus antibody
| Project/Area Number |
25461713
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Dermatology
|
|---|
| Research Institution | Tokyo Dental College |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAGAMI JUN 慶應義塾大学, 医学部, 講師 (80327618)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Keywords | ドラッグデリバリーシステム / 抗体 |
|---|
| 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.
|
| Free Research Field |
皮膚科学
|
