anti-4-1BB Fab/TriCD40L fusion protein IMB071703

A bi-functional fusion protein consisting of a monovalent Fab fragment directed against 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9) fused to a CD40 ligand (CD40L; CD154; TRAP; TNFSF5) trimer, triCD40L, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-4-1BB Fab/triCD40L fusion protein IMB071703 selectively targets and binds to both 4-1BB expressed on T cells and natural killer (NK) cells, and CD40 expressed on antigen-presenting cells (APCs), including dendritic cells (DC), B cells, T cells, and NKs. The trimeric binding of CD40L to CD40 (tumor necrosis factor receptor superfamily member 5; TNFRSF5) induces CD40 trimerization and crosslinking, activates CD40, increases CD40-mediated signaling and specifically induces proliferation and activation of DCs. The CD40 crosslinking leads to 4-1BB receptor clustering, and the Fab fragment binding to 4-1BB activates 4-1BB-mediated signaling, induces cytotoxic T-lymphocyte (CTL) proliferation, cytokine production and promotes a CTL-mediated anti-tumor immune response as well as NK-mediated tumor cell killing in the tumor microenvironment (TME). 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, and T-cell memory formation. CD40, a costimulatory cell surface receptor that belongs to the TNF receptor family, plays a key role in DC maturation, and activation of antigen-specific T cells.