[1PS-094]
우수논문발표상 응모자Tumor-Selective De-Masking of Checkpoint Antibodies to Mitigate irAEs and Sustain Anti-Tumor Immunotherapy
발표자이창현 (성균관대학교)
연구책임자박재형 (성균관대학교)
Abstract
Immune checkpoint blockade (ICB) antibodies offer durable responses, but their clinical use is often limited by immune-related adverse events (irAEs) from off-tumor immune activation. To overcome this limitation, we developed a generalized masking strategy utilizing polyethylene glycol (PEG) conjugation through CDM linkers. This design suppresses antibody-immune cell interactions under physiological pH, thereby reducing systemic immune activation and mitigating irAEs. In mildly acidic tumor microenvironments (TME), PEG is hydrolyzed, reactivating antibody function. In vitro assays confirmed restoration of antigen binding and phagocytic activity. In vivo, this strategy alleviated aCD47-induced anemia and reduced colitis associated with dual ICB therapy. De-masking restored antitumor efficacy and extended survival in syngeneic tumor models. These results highlight the potential of pH-responsive PEGylation as a broadly applicable platform for safer and tumor-selective immunotherapy.