| Project/Area Number |
18591047
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
FUKUDA Tetsuya Tokyo Medical and Dental University, Tokyo Medicl and Dental University Department of Hematolgy, assistant professor (70332624)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | ROR1 / CLL / Wnt5a / immunotherapy / 受容体型チロシンキナーゼ / B細胞腫瘍 |
|---|
| Research Abstract |
We examined the sera of six patients before and after intravenous infusions of autologous chronic lymphocytic leukemia (CLL) cells transduced ex vivo with an adenovirus vector encoding CD154 (Ad-CD154). Following treatment, five patients made high-titer anti-adenovirus antibodies and three made IgG reactive with a leukemia-associated surface-antigen, which we identified as ROR1. Anti-ROR1 antibodies reacted specifically only with the CLL cells of all patients examined (N = 69), but not with normal adult tissues or blood mononuclear cells, including CD5-positive B cells of healthy adults. We found that ROR1 is a receptor for Wnt5a, which could induce activation of NF-kB when co-expressed with ROR1 in HEK293 cells and enhance survival of CLL cells in vitro, an effect that could be neutralized by post-treatment anti-ROR1 antisera. This study indicates that ROR1 is a tumor-associated survival-signaling receptor for Wnt5a that can be targeted by the antibody response to autologous Ad-CD 154-transduced CLL cells.
|
