Application of Engineered NK-92 Cell Extracellular Vesicles in the Treatment of Systemic Lupus Erythematosus
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Introduction
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by loss of immune tolerance, autoantibody production, and multi-organ damage. Current therapies, including glucocorticoids and CAR-T/CAR-NK cell therapies, are limited by adverse effects, high cost, and safety concerns.
Objectives
To develop engineered NK-92 cell-derived extracellular vesicles displaying CD19 single-chain variable fragment (V-CD19-Exo) and evaluate their therapeutic efficacy in an MRL/lpr mouse model of SLE.
Methods
The CD19scFv-LAMP-2B fusion construct was stably expressed in NK-92 cells via lentiviral transduction. Extracellular vesicles were isolated by differential centrifugation and characterized by NTA, TEM, and Western Blot. In vivo efficacy was assessed in MRL/lpr mice through B cell depletion analysis, renal function monitoring, cytokine profiling, autoantibody detection, and survival observation.
Results
V-CD19-Exo significantly reduced splenic CD19□CD20□ B cells from 10.53% to 1.51% (p < 0.0001). Treatment attenuated proteinuria, ameliorated lupus nephritis pathology, reversed splenomegaly, and downregulated serum IgE, IL-17A, IFN-γ, anti-dsDNA, and ANA levels. Notably, V-CD19-Exo improved survival to approximately 80% compared to 25% in untreated controls.
Conclusion
Engineered NK-92 cell-derived extracellular vesicles represent a novel, safe, and effective cell-free therapeutic strategy for SLE, offering advantages over conventional cell therapies including lower immunogenicity, scalable production, and no requirement for lymphodepletion.
