In Search of Better Peptide-(Derived from PD-L2)-Based Immune Checkpoint Inhibitors.

ABSTRACT: Current anti-cancer immune checkpoint therapy relies on antibodies that primarily target the PD-1/PD-L1(-L2) negative regulatory pathway. Although very successful in some cases for certain cancers, these antibodies do not help most patients who, presumably, should benefit from this type of therapy. Therefore, an unmet clinical need for novel, more effective drugs targeting immune checkpoints remains. We have developed a series of high-potency peptide inhibitors interfering with PD-1/PD-L1(-L2) protein-protein interaction. Our best peptide inhibitors are 12 and 14 amino acids long and show sub-micromolar IC₅₀ inhibitory activity in the in vitro assay. The positioning of the peptides within the PD-1 binding site is explored by extensive modeling. It is further supported by 2D NMR

SUBMITTER: Klebansky B 

PROVIDER: S-EPMC11118832 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature