Fully Human Anti-PD-L1 Antibodies with Tumor Cytotoxicity from SmocMab Mice

PD-L1 is highly expressed across a broad spectrum of tumor cells and negatively regulates the tumor cytotoxicity of T cells. Herein, we generated multiple fully human anti-PD-L1 antibodies with high binding affinity through single B cell screening, utilizing SmocMab mice humanized for the variable regions of immunoglobulin heavy and light chains. These antibodies effectively blocked the PD-1/PD-L1 interaction in vitro and exhibited potent endocytic activity. In in vivo studies, monotherapy with the anti-PD-L1 antibodies demonstrated significant tumor-suppressive effects in hPD1 C57BL/6 mice. Furthermore, PD-L1 antibody-drug conjugates (ADCs) constructed based on these anti-PD-L1 antibodies substantially enhanced tumor-killing efficacy. Collectively, these findings validate that SmocMab mice serve as a robust platform for the screening of fully human antibodies with promising therapeutic potential. Citation Format: Ningning Ge, Huacheng He, Lei Ci, Ruilin Sun, Dongxiao Feng. Fully human anti-PD-L1 antibodies with tumor cytotoxicity: Screening in SmocMab mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 968.