Production of a biosimilar version of aflibercept to improve VEGF blocker cytotoxicity on endothelial cells.

This project aimed to produce a biosimilar version of aflibercept (AFL) and evaluate the effect of the co-treatment of AFL with other vascular endothelial growth factor (VEGF) blocker drugs. For this purpose, the optimized gene was inserted into the pCHO1.0 plasmid and transfected into the CHO-S cell line. The final concentration of biosimilar-AFL for the selected clone was 782 mg/L. Results revealed that the inhibition potential of the biosimilar-AFL on HUVEC cells was significant at 10 and 100 nM concentrations and in a dose-dependent manner. Furthermore, co-treatment of biosimilar-AFL with Everolimus (EVR), Lenvatinib (LEN), and Sorafenib (SOR) could reduce HUVEC cell viability/proliferation, more than when used alone. When LEN and SOR were co-treated with biosimilar-AFL, their cytotoxicity increased 10-fold. The most and least efficient combination was seen when biosimilar-AFL combined with LEN and EVR, respectively. Finally, biosimilar-AFL may improve the efficiency of LEN, EVR, and SOR in reducing the VEGF effect on endothelial cells.