Generation and characterization of a functional Nanobody against the vascular endothelial growth factor receptor-2; angiogenesis cell receptor.
Vascular endothelial growth factor receptor-2 (VEGFR2) is an important tumor-associated receptor and blockade of the VEGF receptor signaling can lead to the inhibition of neovascularization and tumor metastasis. Nanobodies are the smallest intact antigen binding fragments derived from heavy chain-only antibodies occurring in camelids. Here, we describe the identification of a VEGFR2-specific Nanobody, named 3VGR19, from dromedaries immunized with a cell line expressing high levels of VEGFR2. We demonstrate by FACS, that 3VGR19 Nanobody specifically binds VEGFR2 on the surface of 293KDR and HUVECs cells. Furthermore, the 3VGR19 Nanobody potently inhibits formation of capillary-like structures. These data show the potential of Nanobodies for the blockade of VEGFR2 signaling and provide a basis for the development of novel cancer therapeutics.
Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran.
Mahdi
M
Behdani
Sirous
S
Zeinali
Hossein
H
Khanahmad
Morteza
M
Karimipour
Nader
N
Asadzadeh
Keyhan
K
Azadmanesh
Alireza
A
Khabiri
Steve
S
Schoonooghe
Mahdi
M
Habibi Anbouhi
Gholamreza
G
Hassanzadeh-Ghassabeh
Serge
S
Muyldermans
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D002161:Camelids, New World; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D020349:Surface Plasmon Resonance; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D007106:Immune Sera; D057127:Single-Chain Antibodies; D040301:Vascular Endothelial Growth Factor Receptor-2