Discovery of TIGIT inhibitors by phage display

Abstract TIGIT is an emerging immune checkpoint receptor expressed higher than PD-1 in some tumors especially anti-PD1 resistant tumors. By competing with the co-stimulatory CD226/DNAM-1 for binding to CD155/PVR, transduces inhibitory signals and suppresses response. Therefore, we sought discover inhibitors improving tumor immunotherapy. Through directional cloning, bacterial transformation phage amplification techniques, generated a novel genetically encoded, phage-displayed bicyclic peptide library comprised of more million sequences. Depending on two combinations different disulfide bonds, each backbone predicted be folded into either endo-bicyclic or exo-bicyclic structure. We conducted three rounds display panning against recombinant IgV domain that enriched high-affinity peptides identified promising peptides. Phage ELISA showed phage-presented competitive evaluated ability disrupt interactions between PVR. This work validated efficiency discovery ligands targeting protein receptors led identification inhibitors. AAI Careers Immunology Fellowship