Anti-VEGFR2 [IMC-1121B (Ramucirumab)]

Absolute Antibody

Anti-VEGFR2 [IMC-1121B (Ramucirumab)]

7

The antibody blocked the VEGFR2/VEGF interaction with an IC50 value of 1 nM and 0.8 nM for Fab and IgG1 fragments respectively. The binding affinity of the Fab and IgG fragments to VEGFR-2 was measured by surface plasmon resonance (Kd= 100 pM and 50 pM respectively). The IgG1 fragment was able to inhibit VEGF-stimulated VEGFR2 phosphorylation in endothelial cells. The epitope mapping of this antibody demonstrated the antibody interacted with the third immunoglobulin domain within the extracellular region of VEGFR2 (Lu et al, 2003; pmid:12917408). The antibody (IgG1) strongly inhibited VEGF-induced migration of human leukemia cells in vitro, and when administered in vivo, significantly prolonged survival of NOD-SCID mice inoculated with human leukemia cells. (Zhu et al, 2003; pmid:12646950). The Fab fragment was able to strongly block VEGFR2/VEGF interaction, resulting in potent inhibition of an array of biological activities of VEGF, including activation of the receptor and its signaling pathway, intracellular calcium mobilization, and migration and proliferation of endothelial cells. (Miao et al., 2006; pmid:16682007). The antibody has demonstrated some antitumor efficacy in humans, including a decrease in tumor vascularity (Spratlin et al, 2010; pmid:21222245). The structure of the Fab fragment alone and in complex with domain 3 of VEGFR2 was determined (Franklin et al, 2011; pmid:21827946).

Flow Cytometry, ImmunoHistoChemistry, Other Application

FC; IHC; crystallography; in vitro; in vivo; therapeutic

Research Use Only

Monoclonal

IMC-1121B (Ramucirumab)

KDR

kinase insert domain receptor

CD309; fetal liver kinase-1; FLK1; kinase insert domain receptor (a type III receptor tyrosine kinase); protein-tyrosine kinase receptor Flk-1; soluble VEGFR2; tyrosine kinase growth factor receptor; vascular endothelial growth factor receptor 2; VEGFR; VEGFR2

Human

IgG1

Vascular endothelial growth factor receptor 2

This reformatted human antibody was made using the variable domain sequences of the original Human Fab format for improved compatibility with existing reagents assays and techniques.

Human

The original antibody was generated by using phage display technology. A new library comprising the single VH paired with the variable light chain (VL) repertoire obtained from the original naıve human library was constructed, followed by phage display-based selection.

-20°C,2°C to 8°C

12352203