PSMA-Targeting Chimeras for Cell-Type-Specific Degradation of Surface Immune Checkpoint Protein PD-L1.

ABSTRACT: Lysosome-targeting chimera technology has been utilized to degrade proteins of interest via the endosome-lysosome pathway mediated by endogenous ligands that engage cell-surface transmembrane proteins. Despite their promising potential, current approaches remain limited by the tissue-specific expression of surface receptors required for endocytosis. Prostate-specific membrane antigen (PSMA) is highly and specifically expressed in prostate cancer, driving significant progress in PSMA-targeted therapies, particularly radioligand therapy and antibody-drug conjugates, through PSMA-mediated internalization. Leveraging this phenomenon, we developed PSMA-targeting chimeras (PATACs), a novel and readily accessible class of heterobispecific small molecules designed for membrane protein degradation.

SUBMITTER: Luo Y 

PROVIDER: S-EPMC12848674 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature