Anti-Human VEGF-A (Ranibizumab) (V202-GRP)

Vascular endothelial growth factor (VEGF), a potent proangiogenic cytokine1, is the key signal used by oxygen-hungry cells to promote the growth of blood vessels. VEGF binds to specialized receptors on the surfaces of endothelial cells and directs them to build new vessels2. VEGF are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood- vessel formation in the adult (angiogenesis). Abnormal VEGF function is associated with inflammatory diseases including atherosclerosis and hyperthyroidism3,4,5,6. VEGF-A is a member of the VEGF gene family, and several isoforms can be generated by alternative splicing7. Additionally, VEGF-A is a major mediator of angiogenesis and plays a key role in various ophthalmic conditions, including age-related macular degeneration8. Ranibizumab is a high-affinity recombinant, humanized antibody that neutralizes all isoforms of VEGF-A8,9. Ranibizumab was derived from a murine monoclonal anti-VEGF antibody10and consists of a nonbinding human sequence and a high affinity murine binding epitope11. When injected intravitreously, ranibizumab can penetrate the internal limiting membrane and access the subretinal space. Ranibizumab reduces the proliferation of endothelial cells as well as vascular permeability and formation of new blood vessels by preventing VEGF-A from interacting with its receptors on the endothelial cell surface9. Ranibizumab is also able to inhibit human umbilical vein endothelial cell proliferation in vitro. Ranibizumab does not bind to mouse VEGF-A in vitro by Western blot, nor does it have a measurable biological effect after intraperitoneal or intravitreal injection in oxygen-induced-retinopathy mouse models12. Intravitreal injections of ranibizumab in cynomolgus monkeys reduces choroidal neovascularization11. Ranibizumab is also known as RhuFab V2 in the literature10.