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Recombinant human anti-vascular endothelial growth factor (VEGF) is a biotechnologically engineered monoclonal antibody designed to inhibit the activity of VEGF, a key molecule involved in angiogenesis. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a critical process in both normal physiological conditions and pathological states, such as cancer.
VEGF is a signal protein that stimulates the growth of blood vessels. It plays a pivotal role in both normal and pathological angiogenesis. VEGF is produced by cells that are deprived of oxygen, a condition known as hypoxia. It binds to VEGF receptors on the surface of endothelial cells, triggering a cascade of events that lead to the formation of new blood vessels. VEGF is crucial for wound healing and the formation of the circulatory system during embryonic development. However, its overexpression is associated with diseases such as cancer, where it promotes tumor growth by supplying nutrients and oxygen through the blood vessels .
The development of anti-VEGF therapy began with the understanding that inhibiting VEGF could potentially halt the growth of tumors by cutting off their blood supply. This led to the creation of monoclonal antibodies that specifically target VEGF. One of the first and most well-known anti-VEGF therapies is bevacizumab, a humanized monoclonal antibody that binds to VEGF and prevents it from interacting with its receptors on endothelial cells .
Recombinant human anti-VEGF antibodies are produced using recombinant DNA technology. This involves inserting the gene that encodes the anti-VEGF antibody into a host cell, such as a Chinese hamster ovary (CHO) cell, which then produces the antibody. The antibody is then purified and formulated for therapeutic use. These antibodies are designed to have high affinity for VEGF, ensuring that they effectively neutralize the protein and inhibit angiogenesis .
The primary mechanism of action of recombinant human anti-VEGF antibodies is the inhibition of VEGF binding to its receptors, VEGFR-1 and VEGFR-2, on the surface of endothelial cells. By blocking this interaction, the antibodies prevent the downstream signaling pathways that lead to endothelial cell proliferation, migration, and new blood vessel formation. This results in the inhibition of angiogenesis, which is particularly beneficial in the treatment of cancers and other diseases characterized by excessive blood vessel growth .
Recombinant human anti-VEGF therapies have been approved for the treatment of various cancers, including metastatic colorectal cancer, non-small cell lung cancer, and glioblastoma. They are also used in the treatment of age-related macular degeneration (AMD), a leading cause of blindness in the elderly, where abnormal blood vessel growth in the retina leads to vision loss .