Abstract 600: Discovery of a single-domain antibody fragment targeting PD-L1 for cancer immunotherapy

Abstract

Abstract Immunotherapy has shown enormous promise for cancer treatment. The use of Antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in cancer immunotherapy. Single-domain antibody fragment (sdAb) is an antibody fragment composed of a single variable domain of the heavy chain. sdAb is the smallest antibody fragment (15 kDa) that maintains the similar antigen-binding affinity. sdAbs show many advantages over monoclonal antibodies such as small size, low immunogenicity, ease of production, and ease of modification, making sdAbs promising candidates for cancer immunotherapy. Here, we use a phage display library to identify an anti-PD-L1 sdAb (CLV3) which effectively blocks the PD-1/PD-L1 interaction. The CLV3 sdAb demonstrates high binding affinity and specificity to PD-L1 protein and PD-L1 overexpression DU145 tumor cells. Moreover, the CLV3 sdAb exhibits efficient tumor penetration in a 3D tumor spheroid model, suggesting its good penetration capability in the tumor microenvironment in vivo. CLV3 restores T cell proliferation and reduces T cell apoptosis in the co-culture experiment of peripheral blood mononuclear cells (PBMC) with tumor cells. These data suggest that the CLV3 sdAb can be potentially used as an anti-PD-L1 inhibitor for cancer immunotherapy. Citation Format: Yanli Liu, Hao Liu, Kun Cheng. Discovery of a single-domain antibody fragment targeting PD-L1 for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 600.