CD74-Targeting Antibody-Drug Conjugate Enhances Immunosuppression of Glucocorticoid in Systemic Lupus Erythematosus.

ABSTRACT: 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 show

SUBMITTER: Du Q 

PROVIDER: S-EPMC12692655 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature