Programmed cell death ligand 1 (PD-L1), one of the key inhibitory immune checkpoint ligand, is often overexpressed on the surface of tumor cells, such as melanoma, ovarian and lung cancers. Its receptor programmed cell death 1 (PD-1) is expressed on the surface of activated T cells. Interaction between PD-L1 and PD-1 transmits negative regulatory signals to T cells. Then it suppresses T-cell activity, promotes apoptosis, and lead to exhaustion of T cells. As a result, the PD-L1/PD-1 interaction allows tumors to be avoided from immune recognition and T cell attack.
However, blocking the interaction between PD-L1 and PD-1 restore T cell activation and function against tumor cells. Recently, several monoclonal antibodies that block the PD-L1/PD-1 pathway, such as nivolumab, pembrolizumab, and atezolizumab, have been approved by the FDA because of their remarkable results. Although these antibodies are reported to have clinical effects, a number of disadvantages still remain, such as high production costs, poor tumor penetration and low oral bioavailability. Compared to antibodies, peptides have several advantages, including lower production costs, better tumor penetration and ease of chemical synthesis.
Here we report the novel PD-L1-binding unnatural cyclic peptide selected by PURE system-based mRNA display evolution via genetic code expansion.