| CD74-Targeting Antibody-Drug Conjugate Enhances Immunosuppression of Glucocorticoid in Systemic Lupus Erythematosus |
| 论文作者 |
Du, QZ; Yao, ST; Huang, YY; Zhang, J; Sonam, W; Lu, X; Yang, JC; Cheng, SP; Wang, R; Xu, JF; Ma, LY; Liu, Y; Wu, GH; Zhang, J; Wang, XL; Lu, W; Ling, ZY; Yi, CY; Sun, B |
| 期刊/会议名称 |
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES |
| 论文年度 |
2025 |
| 论文类别 |
|
| 摘要 |
Glucocorticoid drugs (GCs), while effective in systemic lupus erythematosus (SLE), cause severe systemic side effects due to lack of tissue-specificity. To overcome this bottleneck, we developed a CD74-directed antibody-drug conjugate (Bud-ADC) to deliver budesonide, a potent GC drug, selectively to target CD74-expressing immune cells (e.g., B cells, dendritic cells), which play an important role in SLE pathogenesis. Bud-ADC combines a cross-species anti-CD74 antibody with budesonide via a cleavable linker, enabling immunosuppression on targeted cells. In vitro, Bud-ADC selectively inhibited CD74-high immune cell activation and cytokine production. In two SLE mouse models, Bud-ADC significantly alleviated disease hallmarks-reducing autoantibodies, splenomegaly, and kidney damage-while showing superior efficacy to free budesonide at equivalent doses. The therapeutic effects involved both direct targeting of CD74-high immune cells and indirect modulation of T cell responses despite low CD74 expression. This study establishes CD74-targeted ADC as a novel strategy to enhance GC efficacy in SLE, aiming at minimizing off-target toxicity while maintaining broad immunosuppressive activity. The translatable design supports further preclinical and clinical development for autoimmune diseases. |
| 卷 |
26 |
| 影响因子 |
4.9 |
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