Definition

A bispecific agent composed of a human immunoglobulin G4 (IgG4) monoclonal antibody targeting the cell surface antigen cluster of differentiation (CD228; melanotransferrin; MFI2; MELTF; p97) fused to a binding protein targeting the costimulatory receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9), with potential immunostimulating and antineoplastic activities. Upon administration, anti-CD228/4-1BB bispecific agent SGN-BB228 simultaneously targets and binds to CD228 expressed on the surface of tumor cells and 4-1BB expressed on a variety of leukocyte subsets including activated T-lymphocytes. This crosslinks CD228-expressing tumor cells and 4-1BB-expressing T-cells, and activates 4-1BB signaling locally in the tumor microenvironment (TME). This results in cytotoxic T-cell co-stimulation, enhances T-lymphocyte-mediated anti-tumor activity and leads to cytotoxic T-cell-mediated lysis of CD228-expressing tumor cells. CD228, a cell-surfaced, glycosylphosphatidylinoitol (GPI)-anchored glycoprotein that belongs to the transferrin family of iron-binding proteins, is upregulated in certain tumor types including melanoma, mesothelioma and lung cancer. 4-1BB, a surface glycoprotein of the tumor necrosis factor receptor superfamily, is an inducible costimulatory receptor that plays a key role in T-cell proliferation, survival and cytolytic activity.