Definition

A bispecific antibody targeting both CD137 (4-1BB; tumor necrosis factor receptor superfamily member 9; TNFRSF9) and fibroblast activation protein (FAP), with potential immunomodulating and antineoplastic activities. Upon administration, anti-CD137/anti-FAP bispecific antibody BI 765179 targets and binds to both FAP, expressed on cancer-associated fibroblasts (CAFs) in the tumor stroma, and CD137, expressed on the surface of immune cells including activated T-lymphocytes, natural killer (NK) cells and dendritic cells (DCs). The simultaneous binding of FAP and CD137 results in local clustering of FAP-expressing CAFs and CD137-expressing T cells in the tumor microenvironment (TME), local immune cell activation through the promotion of T-cell activation and cytokine release, and T-cell-mediated anti-tumor immune responses. CD137, 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. FAP, a membrane-bound serine protease overexpressed on CAFs, is minimally expressed on normal, healthy cells.