Definition

A recombinant bifunctional fusion protein composed of a humanized immunoglobulin (Ig) G1 anti-programmed death ligand 1 (PD-L1) monoclonal antibody fused to the extracellular domain (ECD) of the human transforming growth factor beta (TGFbeta) receptor type II (TGFbetaRII), with potential antineoplastic and immune checkpoint modulating activities. Upon administration of anti-PD-L1/TGFbetaRII fusion protein BJ-005, the TGFbetaRII moiety targets, binds to and neutralizes TGFbeta while the antibody moiety simultaneously targets, binds to, and inhibits the activity of PD-L1 on the tumor cell. This prevents both TGFbeta- and PD-L1-mediated immuno-suppressive pathways signaling, and increases natural killer (NK) cell and cytotoxic T-lymphocyte (CTL) activities. This restores and enhances anti-tumor responses and inhibits tumor cell proliferation in susceptible tumor cells. TGFbeta and PD-L1 are both upregulated in certain types of cancers and and play key roles in tumor immune suppression; their overexpression is associated with increased evasion of immune surveillance and contributes to poor prognosis.