Fully human anti-PD-L1 antibodies with tumor cytotoxicity: Screening in 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.