Fig 1. An autologous hinge as an Ab lock to enhance the selectivity and maintain the host immunity of Infliximab.

We used an autologous IgG1 hinge as Ab lock to cover the antigen-binding site of Infliximab by using MMP-2/9 substrate linker to generate pro-Infliximab. Upon protease activation at the RA region, the Ab lock was released, and the pro-Infliximab could specifically activate and neutralize TNFα at the disease site to inhibit RA progression. Ab, antibody; IgG1, immunoglobulin G1; MMP, matrix metalloproteinase; RA, rheumatoid arthritis; TNFα, tumor necrosis factor α.