Anti-hVEGF-hIgG1 features the constant region of the human IgG1 isotype and the variable region of bevacizumab. Bevacizumab is a humanized IgG1 monoclonal antibody that targets VEGF, a signaling protein that promotes the growth of new blood vessels. In many cancers VEGF is overexpressed, thereby promoting tumor growth and angiogenesis. The overexpression of VEGF can also lead to vascular disease, particularly in the retina [1]. Bevacizumab neutralizes VEGF and blocks its signal transduction through the VEGF receptors [2, 3]. Consequently, bevacizumab blocks downstream pathways which regulate cell growth and angiogenesis. Bevacizumab displays no antibody-dependent cell-mediated cytotoxicity (ADCC) [4]. Bevacizumab has been approved by the FDA for the treatment of certains types of brain, colorectal, lung, kidney, and ovarian cancers.
Human IgG1 is the most abundant immunoglobin present in serum and binds with high affinity to the Fc receptor on phagocytic cells. The human IgG1 isotype displays high ADCC and complement dependent cytotoxicity (CDC).
Anti-hVEGF-hIgG1 was generated by recombinant DNA technology. It has been produced in CHO cells and purified by affinity chromatography with protein G.
References:
- Ablonczy Z. et al., 2014. Progressive dysfunction of the retinal pigment epithelium and retina due to increased VEGF-A levels. FASEB J. 28:2369-79.
- Papadopoulos N. et al., 2012. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 15(2):171-85.
- Ferrara N. et al., 2004. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 3(5):391-400.
- Damiano V. et al., 2007. TLR9 agonist acts by different mechanisms synergizing with bevacizumab in sensitive and cetuximab-resistant colon cancer xenografts. PNAS. 104(30):12468-73.