Innovations in cancer immunotherapy with PD-1 antibody-drug conjugates and their antitumor mechanisms. (2025)

Antibody-drug conjugates (ADCs) targeting programmed death-1 (PD-1) represent a novel class of cancer immunotherapies that combine immune checkpoint blockade with targeted delivery of cytotoxic agents. By selectively binding PD-1-expressing cells within the tumor microenvironment, PD-1 ADCs aim to reverse T cell exhaustion and eliminate immunosuppressive cells while directly inducing tumor cell death. This dual mechanism enhances antitumor immunity and addresses resistance associated with conventional PD-1 inhibitors. Despite promising preclinical results and emerging clinical data, challenges such as tumor antigen heterogeneity, resistance development, and linker stability remain. Future innovations in ADC engineering, payload optimization, and combination therapies hold potential to over