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          Document History for Document ID 199065

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Document Version Version Comment Date Status
199065.0 [No comment] 31.03.2011 11:36 Released

ID: 199065.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Biopanning of single-chain antibodies expressing phages reveals distinct expression patterns of angiogenic and arteriogenic vessels
Authors:Mazur, A.; Deylig, A.; Schaper, W.; Meinertz, T.; Ito, W. D.
Date of Publication (YYYY-MM-DD):2003
Title of Journal:Endothelium
Volume:10
Issue / Number:4-5
Start Page:277
End Page:284
Review Status:not specified
Audience:Not Specified
Abstract / Description:"Therapeutic angiogenesis" requires targeted delivery of growth factors for maximal benefit and limitation of potential hazards such as enhancement of tumor or plaque angiogenesis. Physiological distinctions between angiogenesis and collateral growth suggest the possibility of targeting selectively collateral endothelium. This article describes the generation of collateral-targeting single-chain antibodies (scFv). Membrane preparations of growing collateral arteries from rats were used to produce collateral-targeting antibodies (CTAs) via immunization of mice. ScFv were generated from CTA-producing hybridoma and cloned into the pV gene of M13 phages. Phages expressing collateral-targeting scFv (CT scFv) were selected via repeated exposure to activated collateral arteries followed by reamplification. CT scFv could specifically be amplified, selected, and sequenced. Phages expressing CT scFv bound selectively to proliferating collateral vessels as identified by positive Polycyclic Nuclear Antigen (PCNA) staining and homed specifically to collateral endothelium after in vivo injection but bound neither to control vessels nor to tumor vessels. This study reveals major differences between angiogenic and collateral endothelium and delivers a tool that will allow the stimulation of collateral growth without promoting tumor or plaque angiogenesis.
Free Keywords:Amino Acid Sequence
; Animals
; Antibodies, Monoclonal/*genetics/metabolism
; Arteries/*growth & development/metabolism
; Bacteriophage M13/genetics
; Cell Adhesion Molecules/genetics/metabolism
; Cell Line
; Collateral Circulation
; Endothelial Cells/metabolism
; Femoral Artery/growth & development
; Gene Expression Regulation
; Genetic Vectors
; Mice
; Molecular Sequence Data
; *Neovascularization, Physiologic
; Oligopeptides/genetics/immunology
; Peptide Library
; Rats
; Rats, Sprague-Dawley
; Support, Non-U.S. Gov't
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=... [ID No:1]