Vascular endothelial growth factor A, B and Placental growth factor (VEGF-A/VEGF-B/PlGF)

The target complex comprising Vascular Endothelial Growth Factor A (VEGF-A), Vascular Endothelial Growth Factor B (VEGF-B), and Placental Growth Factor (PlGF) is a central regulator of both physiological and pathological angiogenesis and vascular permeability (Papadopoulos et al., 2012, Angiogenesis). These secreted glycoproteins function by binding to and activating specific tyrosine kinase receptors, primarily VEGFR-1 and VEGFR-2, on the surface of endothelial cells (Holash et al., 2002, PNAS). In diseases such as neovascular age-related macular degeneration (nAMD) and various malignancies, the over-expression of these ligands leads to the formation of fragile, leaky blood vessels and promotes tumor growth (Stewart, 2012, Nature Reviews Drug Discovery). Therapeutic intervention is achieved through the use of a recombinant fusion protein, often referred to as a VEGF Trap, which consists of the extracellular binding domains of human VEGFR-1 and VEGFR-2 fused to an IgG1 Fc fragment (FDA Label: Eylea). This fusion protein acts as a high-affinity soluble decoy receptor that sequesters VEGF-A, VEGF-B, and PlGF, effectively neutralizing their biological activity and preventing receptor-mediated signaling (Hecht et al., 2012, Clinical Colorectal Cancer). By inhibiting these pathways, the treatment reduces vascular leakage in the eye and limits blood supply to tumors in oncological settings (NIH PubChem: Aflibercept).

Other names

VEGF TrapVEGF-A/VEGF-B/PlGF signaling complexAflibercept targetVascular endothelial growth factor receptor fusion protein target

The mechanism involves the use of a recombinant fusion protein (VEGF Trap) that acts as a soluble decoy receptor, binding to and neutralizing VEGF-A, VEGF-B, and PlGF ligands with high affinity, thereby preventing their interaction with and activation of endogenous VEGFR-1 and VEGFR-2 receptors (Holash et al., 2002, PNAS; Papadopoulos et al., 2012, Angiogenesis).