Anti-tumor effectiveness of a novel bispecific antibody that blocks both PD-L1 and LAG-3

Over the past few years, substantial progress with promising outcomes were achieved for the use of antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in immunotherapy. However, several issues still limit their effectiveness for anti-cancer therapy. Therefore, we designed a bispecific antibody (referred to as Ba-PL) against PD-L1 and T cell immune checkpoint lymphocyte activation gene-3 (LAG-3), in an attempt to block both targets to further improve immune efficacy against solid tumors. A bispecific T cell engager structure was used to connect the variable regions of the PD-L1 and LAG-3 antibodies in series. The antibody was prepared using a prokaryotic expression system, and its molecular and cellular-level affinity was assessed in vitro. Furthermore, we preliminarily evaluated its anti-tumor effects in mice. Collectively, the antibody prepared using the prokaryotic expression system had preferable tumor cell-targeting ability and blocked the interaction of PD-1 and LAG-3 with their ligands. Further, the results of the animal experiments demonstrated that the Ba-PL exerted a better anti-tumor effect in 4T1 and H22 tumor-bearing mice. Overall, our study suggests that this strategy has therapeutic potential for liver hepatocellular and breast invasive carcinoma.