PC18.1

PC18.1 is a therapeutic peptide inhibitor designed to disrupt the interaction between Claudin 18.2 (CLDN18.2) and β-catenin within CD8+ T cells. Research indicates that CLDN18.2 can be transferred from tumor cells to T cells via trogocytosis, where it binds to β-catenin and recruits the CK1α/GSK3β complex, leading to β-catenin degradation. This process suppresses Wnt/β-catenin signaling and induces metabolic reprogramming characterized by reduced glucose uptake and glycolytic activity, which ultimately impairs T-cell activation and cytotoxic function. PC18.1 blocks the CLDN18.2-β-catenin interface, thereby reversing glycolytic suppression, restoring effector T-cell function, and mitigating systemic immune senescence. In preclinical models of pancreatic ductal adenocarcinoma (PDAC), PC18.1 has demonstrated the ability to inhibit tumor progression and synergize with anti-PD-1 therapy.