Abstract 2394: Discovery of small anti-PD-L1 peptides for cancer immunotherapy

Abstract

Abstract Immunotherapy using checkpoint inhibitors, especially PD-1/PD-L1 inhibitors, has now evolved into the most promising therapy for cancer patients. However, most of these inhibitors are monoclonal antibodies, and their large size may limit their tumor penetration, leading to suboptimal efficacy. As a result, there has been a growing interest in developing low-molecular-weight checkpoint inhibitors. Using a phage display peptide library, we discover small peptide-based anti-PD-L1 inhibitors to block the PD-1/PD-L1 interaction. These peptides exhibit high affinity and specificity to human PD-L1 as well as PD-L1-positive human cancer cells. Molecular docking studies indicate that the CLP002 peptide specifically binds to PD-L1 at the residues where PD-L1 interacts with PD-1. Compared to anti-PD-L1 antibody, the anti-PD-L1 peptides exhibited better tumor penetration in a 3D tumor spheroid model. The CLP002 peptide restores proliferation and prevents apoptosis of T cells that are co-cultured with cancer cells. The CLP002 peptide also inhibits tumor growth and increases survival of CT26 tumor-bearing mice, suggesting that the CLP002 peptide represents a promising low-molecular-weight checkpoint inhibitor for cancer immunotherapy. Citation Format: Hao Liu, Zhen Zhao, Yuanke Li, Kun Cheng. Discovery of small anti-PD-L1 peptides for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2394.