Navicizumab is a bispecific antibody that target Delta-like ligand 4 (DLL4) as well as vascular endothelial growth factor (VEGF).
DLL4 protein is encoded by DLL4 gene and is part of a signaling pathway known as Notch pathway. This pathway is responsible for the development of many tissues. The attachment of DLL4 protein to its receptor, Notch1, launches a series of signaling reactions that affect different cell functions. Furthermore, DLL4 protein is involved in the development of blood vessels before birth and throughout life. In cancer, the notch induced pathway is essential for tumor angiogenesis and the stemness of cancer cells.
VEGF is a sub-family of growth factors also involved in the formation of blood vessels. Indeed, VEGF is a signaling protein in vasculogenesis and angiogenesis. VEGF is important in restoring the oxygen supply to tissues in hypoxic conditions where blood circulation is scarce. VEGF is also responsible for the establishment of new blood vessels following injury. This protein has also been linked to the formation of new blood vessels throughout the embryonic development. Overexpression of VEGF have been linked to several diseases including cancer. In cancer, VEGF upregulation has been linked to metastasis.
Navicizumab inhibits DLL4/VEGF pathway inducing, as a result, a potent anti-tumor response. Furthermore, this therapeutic antibody can mitigate the toxicities related to angiogenesis. The anti-tumor activity of this therapeutic antibody was demonstrated in phase 1a clinical trials for several cancers including ovarian cancer, fallopian tube cancer, solid tumors and peritoneal cancer. The findings from phase Ia trials suggest that the intake of navicizumab is safe and can be administered on a continuous basis.
As per 2019, navicizumab was granted fast grand designation by U.S food and drug industry (FDA) as a potential treatment for heavily pretreated ovarian cancer. The purpose of this designation is to expedite clinical development and review process and facilitate drug entering the market, This product is for research use only.
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