PD-L1 antibody-drug conjugate

PD-L1 antibody-drug conjugates (ADCs) represent an emerging class of oncology therapeutics that combine the targeting specificity of an anti-PD-L1 monoclonal antibody with the potent cytotoxic activity of a chemical payload. PD-L1 (Programmed Death-Ligand 1) is a well-validated immune checkpoint protein frequently overexpressed on various solid tumors to evade immune detection. By targeting PD-L1, these ADCs not only potentially block the PD-1/PD-L1 interaction to reinvigorate T-cell responses but also utilize the protein as a cell-surface anchor for internalization. Once inside the tumor cell, the ADC releases its payload—commonly a microtubule disruptor like monomethyl auristatin E (MMAE) or a topoisomerase I inhibitor—to induce direct cell death. This dual-mechanism approach aims to overcome resistance to standard checkpoint inhibitors and provide a more targeted delivery of chemotherapy, thereby expanding the therapeutic window. Leading candidates in this class include SGN-PDL1V (developed by Seagen/Pfizer) and HLX43 (Henlius), which are being evaluated across a broad range of solid tumors including lung, breast, and head and neck cancers.