Anti-hVEGF-hIgG4 (S228P)

Monoclonal human IgG4 (S228P) antibody against human VEGF

Anti-hVEGF-hIgG4 (S228P) features the constant region of the human IgG4 (S228P) 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.

Anti-hVEGF-hIgG4 (S228P) contains an engineered hinge region mutation (S228P) designed to prevent exchange of IgG4 molecules.

Anti-hVEGF-hIgG4 (S228P) was generated by recombinant DNA technology. It has been produced in CHO cells and purified by affinity chromatography with protein G.

References:

1. 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.
2. 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.
3. 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.
4. 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.