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Phage-derived fully human antibody scFv fragment directed against human vascular endothelial growth factor receptor 2 blocked its interaction with VEGF.
MedLine Citation:
PMID:  22581629     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Vascular endothelial growth factor receptor 2 (VEGFR-2) plays a critical role in tumor angiogenesis. None therapeutic antibodies targeting VEGFR-2 are available in clinical use. Herein, we describe the screening of a new single-chain antibody fragment (scFv) targeting extracellular domain 3 of human VEGFR-2 (KDR3) from Griffin phage display scFv library. A comprehensive sequence analysis was performed to assign the framework and complementary-determining regions. The scFv exerted particular binding sites to KDR3 on Molecular Docking, and the binding affinity was further convinced by binding analysis both in quantitative ELISA and real-time kinetic determination by biosensors (K(D) = 40 nM).Finally, the scFv was revealed to inhibit VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVECs) (IC(50) = 5 nM) and to inhibit HUVEC migration significantly at 17 nM. Taken together, our results indicate that we have successfully isolated a scFv which differentially recognizes KDR3 and has potential clinical applications in the treatment of angiogenesis related diseases. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012.
Authors:
Juan Zhang; Haixin Li; Xiuyun Wang; Haidi Qi; Xiaoniu Miao; Tao Zhang; Guosheng Chen; Min Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-11
Journal Detail:
Title:  Biotechnology progress     Volume:  -     ISSN:  1520-6033     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8506292     Medline TA:  Biotechnol Prog     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Institute of Chemical Engineers (AIChE).
Affiliation:
State Key Laboratory of Natural Medicines, Department of Molecular Biology, China Pharmaceutical University, Nanjing 210009, China. juancpu@126.com.
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