Effect of single-chain antibody targeting of the ligand-binding domain in the anaplastic lymphoma kinase receptor.
作者： D C Stylianou , A Auf der Maur , D P Kodack , R T Henke , S Hohn
DOI: 10.1038/ONC.2009.184
关键词:
摘要: The tyrosine kinase receptor anaplastic lymphoma (ALK) and its ligand, the growth factor pleiotrophin (PTN), are highly expressed during development of nervous system have been implicated in malignant progression different tumor types. Here, we describe human single-chain variable fragment (scFv) antibodies that target ligand-binding domain (LBD) ALK show effect vitro vivo. LBD was used as a bait yeast two-hybdrid to select scFv from library with randomized complementarity-determining region 3 domains. Surface plasmon resonance showed high-affinity binding selected scFv. anti-ALK competed for PTN intact cells inhibited PTN-dependent signal transduction through endogenous ALK. Invasion an endothelial cell monolayer by U87MG glioblastoma In addition, established xenografts mice reversed after induction conditional expression archival brain tumors levels were found elevated appear correlated poor patient survival. This suggests rate-limiting function PTN/ALK interaction may be exploited therapeutically.
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