TNF and rheumatoid arthritis: As with the activatable bi-specific Ab, the substrate linker of aDVD can also be specifically hydrolyzed by overexpressed protease in the inflamed region, restore the antigen neutralizing ability (e.g., TNF-α or CTLA-4) and potentially enhance the therapeutic index of Ab drugs for the treatment of RA, malignancies and other inflammatory diseases in the future.