Cell子刊：管晓翔/李金波合作开发抗体-PROTAC-偶联物，增强三阴性乳腺癌免疫治疗

TL;DR - Researchers developed ASA, a TROP2-targeted antibody–PROTAC conjugate that degrades BRD4 in triple-negative breast cancer cells. The approach may improve tumor targeting and strengthen anti-PD-L1 immunotherapy while reducing off-target toxicity.

• ASA uses TROP2-mediated internalization and a hypoxia-cleavable linker to deliver a BRD4-degrading PROTAC selectively to tumors.
• Sustained BRD4 degradation suppresses c-Myc and PD-L1 expression, disrupts DNA repair, and inhibits tumor progression.
• ASA showed stronger targeting and antitumor effects than the unconjugated PROTAC component.
• Combining ASA with anti-PD-L1 therapy improved tumor control and promoted CD8+ T-cell infiltration and activation.