FAP/4-1BB-targeting fusion protein RO7122290

A bispecific antibody-like fusion protein consisting of a trimeric ligand for the T-cell co-stimulatory immune receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9) and an antigen-binding fragment (Fab) moiety targeting the tumor-associated protein fibroblast activation protein (FAP), with potential immunomodulating and antineoplastic activities. Upon administration, the FAP/4-1BB-targeting fusion protein RO7122290 targets and binds to both FAP, localized on tumor stromal cells, and 4-1BB, expressed on a variety of leukocyte subsets including activated T lymphocytes and natural killer (NK) cells. The simultaneous binding of FAP and 4-1BB results in local clustering of FAP-expressing tumor stromal cells and 4-1BB-expressing T cells, and local immune cell activation through the promotion of T-cell activation, cytokine release and T-cell-mediated anti-tumor immune responses. 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. FAP is abundantly expressed by cancer-associated fibroblasts in the majority of solid tumors.