anti-GPC3/anti-4-1BB bispecific antibody BGB-B2033

A bispecific antibody directed against both the tumor-associated antigen (TAA) glypican-3 (GPC3; GPC-3) and the costimulatory receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9), with potential immunostimulating and antineoplastic activities. Upon administration, anti-GPC3/anti-4-1BB bispecific antibody BGB-B2033 simultaneously targets and binds to GPC3 expressed on tumor cells and 4-1BB expressed on activated T lymphocytes and natural killer (NK) cells. This crosslinks GPC3-expressing tumor cells and 4-1BB-expressing T-cells and NK 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 GPC3-expressing tumor cells. GPC3, a heparan sulfate proteoglycan and a member of the glypican family, is overexpressed on certain tumor cell types while minimally expressed in normal, healthy cells. GPC3 plays an important role in tumor cell proliferation in various tumor cell types.