Definition

A bifunctional fusion protein composed of an anti-programmed death ligand 1 (PD-L1) monoclonal antibody bound, via the C-terminal ends of the Fc region, to the N-terminal-truncated extracellular domain (ECD) of human transforming growth factor beta (TGFbeta) receptor type II (TGFbetaRII), with potential antineoplastic and immune checkpoint modulating activities. Upon administration, retlirafusp alfa targets, binds to and neutralizes TGFbeta on the tumor cell 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; their overexpression is associated with increased evasion of immune surveillance and contributes to poor prognosis.