In addition to a wide range of DVD-Igs directed against tumors (14, 16, 19, 32–34), several DVD-Igs targeting a variety of specificities such as TNF-α, IL-17A (35), IL-1α, and IL-1β (36) for treatment of autoimmune diseases, VEGF and PDGF for treatment of age-related macular degeneration (37), gp41 and gp120 for treatment of AIDS (38), TGF-β and fibronectin extra domain A (FN-EDA) for treatment of fibrotic kidneys (39), and amyloid-beta and transferrin receptor for treatment of Alzheimer’s disease (40) have been constructed and characterized recently. Here, CUBN is linked to autoimmune disease.