Immune checkpoint targeted drug conjugate therapies: Bridging preclinical and clinical innovation for solid tumor therapy.

Solid tumors remain a significant therapeutic challenge due to their complex biology, heterogeneous tumor microenvironment (TME), and frequent development of resistance to standard treatments. Although immune checkpoint inhibitors (ICIs) have redefined tumor therapy by restoring antitumor immunity, their clinical benefit in Solid tumors is often constrained by low response rates (LRR), immune-related toxicities, and adaptive resistance. Immune checkpoint targeting drug conjugates (IDCs) have recently emerged as an innovative approach that combines checkpoint blockade with the targeted delivery of cytotoxic or immunomodulatory payloads. By employing monoclonal antibodies (MABs) or engineered scaffolds conjugated to potent effector molecules through optimized linker chemistries, IDCs are designed to improve tumor selectivity, reinvigorate T-cell activity, and induce direct tumor cell death. This review outlines the design principles, operational mechanism, and current clinical and preclinical (PC) progress of IDCs in Solid tumors, with emphasis on key targets including PD-L1/PD-1, TIGIT, CTLA-4, and LAG-3. Translational challenges, including safety concerns, resistance pathways, and manufacturing complexities, are also examined, alongside emerging innovations such as bispecific formats and rational combination strategies. Collectively, IDCs represent a promising next-generation modality with the potential to expand durable therapeutic outcomes in solid tumor management.