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영어

Vascular endothelial growth factor (VEGF-A) is a key cytokine in the development of normal blood vessels as well as the development of vessels in tumors and other tissues undergoing abnormal angiogenesis. There are two market‐launched humanized antibodies derived from a common mouse anti‐VEGF antibody - bevacizumab, a full‐length IgG1 approved for the treatment of specified cancer indications, and ranibizumab, an affinity‐matured antibody Fab domain approved for use in age‐related macular degeneration (AMD). In clinical trial, these two anti-VEGF antibodies, bevacizumab (Avastin_ anti-VEGF antibody) and ranibizumab (Lucentis anti‐VEGF antibody), have demonstrated therapeutic utility in blocking VEGF‐induced angiogenesis. Avastin, however, has showed its limitation in expanding its clinical application because of efficacy and safety issues such as hypertension, bleeding, bowel/nasal perforation, thrombotic angiopathy, encephalopathy, coronary/perifheral artery diseases.
With this view, next generation anti‐VEGF antibodies might have improved VEGF affinity or might more efficiently block VEGF activity through binding to a novel epitope. An additional desirable quality for new anti‐VEGF antibodies is an ability to bind both mouse and human VEGF. This allows testing of the antibodies in a greater variety of model systems before progression to primate studies and addresses the contribution of host VEGF to xenograft growth. As an effort to develop a next generation anti‐VEGF antibody to overcome the efficacy and safety limitation of Avastin, fully human antibody F6 has been developed.
The detailed profile of F6 will be introduced. Also the efficacy of F6 antibody was tested in vivo side by side with Avastin, and showed more potent activity to inhibit esophageal cancer growth in regression xenograft model.