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

Abstract

Abstract Over the past few years, significant progress with promising outcomes has been made in the use of antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) for immunotherapy. However, several issues still limit their effectiveness for anti-cancer therapy. Therefore, we designed a bispecific antibody (BsAb) 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. We further constructed a recombinant plasmid and used a prokaryotic expression system to prepare the antibody. The affinity and blocking activities of the antibody was verified using an enzyme-linked immunosorbent assay, and the affinity of the antibody was further verified at the cellular level using flow cytometry and fluorescence microscopy. 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 BsAb exerted a certain anti-tumor effect. Overall, our study suggests that this strategy has therapeutic potential for liver hepatocellular carcinoma and breast invasive carcinoma.