2007 Fiscal Year Final Research Report Summary
The functional analysis of receptor tyrosine kinase, ROR1 in B cell malignancy
| Project/Area Number |
18591047
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
FUKUDA Tetsuya Tokyo Medical and Dental University, Tokyo Medicl and Dental University Department of Hematolgy, assistant professor (70332624)
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| Project Period (FY) |
2006 – 2007
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| Keywords | ROR1 / CLL / Wnt5a / immunotherapy |
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| 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.
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[Journal Article] Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a2008
Author(s)
Fukuda T, Chen L, Endo T, Tang L, Lu D, Castro JE, Widhopf GF 2nd, Rassenti LZ, Cantwell MJ, Prussak CE, Carson DA, Kipps TJ.
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Journal Title
Proc Nat1 Acad Sci USA 105(8)
Pages: 3047-52
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Thymidine-phosphorothioate oligonucleotides induce activation and apoptosis of CLL cells independently of CpG motifs or BCL-2 gene interference2006
Author(s)
Castro JE, Prada CE, Aguillon RA, Kitada S, Fukuda T, Motta M, Wu C, Dicker F, Sun G, Wang JY, Carson DA, Reed JC, Kipps TJ.
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Journal Title
Leukemia 20(4)
Pages: 680-8
Description
「研究成果報告書概要(欧文)」より
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