Fig. 2
From: Ab locks for improving the selectivity and safety of antibody drugs
The autologous hinge domain as a universal Ab lock for enhancing disease site selectivity and minimizing the on-target toxicity of Ab drugs. Lu et al. used an autologous human IgG1 hinge domain as an Ab lock to cover the antigen binding site of a Ab drug (i.e., anti-TNF-α Ab, Infliximab) by using the MMP-2/9 substrate linker to generate a pro-Ab. When the pro-Ab encounters activated protease at the inflamed region (e.g., the RA region), the substrate linker is hydrolyzed, the Ab lock is released, and the pro-Ab can specifically activate and neutralize the target antigen (e.g., TNF-α) at the disease site to inhibit RA progression. Ab, antibody; IgG1, immunoglobulin G1; MMP, matrix metalloproteinase; TNF-α, tumor necrosis factor α