CD155-binding peptide

CD155-binding peptide (CD155pep) is a high-affinity therapeutic peptide identified through phage display technology that targets CD155 (also known as Poliovirus Receptor or PVR). CD155 is an immunoglobulin-like protein frequently overexpressed in various malignancies, including colon cancer, where it acts as an immunosuppressive ligand by binding to TIGIT and CD96 on immune cells, thereby outcompeting the activating receptor CD226. CD155pep works by binding to CD155 on tumor cells, leading to its downregulation and disrupting the inhibitory CD155-TIGIT/CD96 signaling axis. This mechanism enhances the antitumor activity of CD8+ T cells, increasing the secretion of Granzyme B, Interferon-gamma (IFN-γ), and Tumor Necrosis Factor-alpha (TNF-α). Furthermore, the peptide modulates the tumor microenvironment by shifting macrophage polarization toward a pro-inflammatory state, characterized by increased IL-12 and decreased IL-10 production. A derivative form, CD155pep-linked lytic peptide, has also been developed to provide selective direct cytotoxicity against CD155-high tumor cells.