VEGF-Trap is a potent VEGF blocker with enhanced pharmacokinetic properties, designed to suppress tumor growth and vascularization. The study aimed to optimize the VEGF-blocking pathway by creating a soluble decoy receptor that prevents VEGF from binding to its normal receptors. The highest-affinity VEGF blocker, a soluble decoy receptor fusing the first three Ig domains of VEGF receptor 1 to an Ig constant region, had poor in vivo pharmacokinetic properties. By engineering variants of this receptor, the researchers developed VEGF-TrapAB2, which reduced the positive charge and improved its pharmacokinetic profile. This variant showed significantly higher binding affinity to VEGF and was effective in blocking VEGF-induced cell proliferation and angiogenesis in vitro and in vivo. VEGF-TrapAB2 also demonstrated superior efficacy compared to a monoclonal antibody targeting VEGF receptor 2 in inhibiting tumor growth in various models. The engineered VEGF-Trap is currently in clinical trials for cancer treatment, showing promise as a potent and safe anti-angiogenic agent.VEGF-Trap is a potent VEGF blocker with enhanced pharmacokinetic properties, designed to suppress tumor growth and vascularization. The study aimed to optimize the VEGF-blocking pathway by creating a soluble decoy receptor that prevents VEGF from binding to its normal receptors. The highest-affinity VEGF blocker, a soluble decoy receptor fusing the first three Ig domains of VEGF receptor 1 to an Ig constant region, had poor in vivo pharmacokinetic properties. By engineering variants of this receptor, the researchers developed VEGF-TrapAB2, which reduced the positive charge and improved its pharmacokinetic profile. This variant showed significantly higher binding affinity to VEGF and was effective in blocking VEGF-induced cell proliferation and angiogenesis in vitro and in vivo. VEGF-TrapAB2 also demonstrated superior efficacy compared to a monoclonal antibody targeting VEGF receptor 2 in inhibiting tumor growth in various models. The engineered VEGF-Trap is currently in clinical trials for cancer treatment, showing promise as a potent and safe anti-angiogenic agent.