Antibody phage display technologies with special reference to angiogenesis.
The presence of blood vessels is a prerequisite for normal development, tissue growth, and tissue repair. However, its abnormal occurrence or absence can also potentiate disease processes. Angiogenic therapies have been used to stimulate blood vessel growth in ischemic conditions such as severe end-stage peripheral vascular disease, ischemic heart disease and stroke and for inhibition of angiogenesis in tumors. The targeting and identification of novel endothelial cell (EC) markers that can ultimately be used in angiogenic strategies is an expanding field but is limited by the availability of reagents. For instance repeated injection of mouse monoclonal antibodies (Mabs) against angiogenic EC, can result in the production of autoantibodies. Therefore, these mouse Mabs cannot be used for therapeutic purposes. Phage display technology was employed in this context to select antibodies, proteins, and peptides against known or novel EC antigens. Furthermore, technologies have been developed that enable the specific targeting of epitopes on cells including the endothelium with high-affinity/avidity antibodies. The focus for these antibody targeting strategies are markers that are unique or up-regulated on angiogenic EC including the vascular endothelial growth factor receptor (VEGFR) KDR, endoglin (CD105), and the extracellular domain B (ED-B) domain of fibronectin (FN). These markers are reviewed herein.
Smith
Julia
J
University of Manchester, Stopford Building, Oxford Rd, Manchester, M13 9PT, UK. Jusmith@fs1.scg.man.ac.uk
Kontermann
Roland E
RE
Embleton
Jim
J
Kumar
Shant
S
D043925:Angiogenesis Inducing Agents / Q000009:adverse effects / Q000627:therapeutic use; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD; D000071063:Endoglin; D042783:Endothelial Cells / Q000276:immunology; D005353:Fibronectins / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D051379:Mice; D018919:Neovascularization, Physiologic; D019151:Peptide Library; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000941:Antigens; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; C067625:FN1 protein, human; D005353:Fibronectins; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D019151:Peptide Library; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; C055966:immunoglobulin Fv; D040301:Vascular Endothelial Growth Factor Receptor-2