Prevention of acute graft-versus-host disease via single-dose administration of bioengineered extracellular vesicles [scRNA-seq]

We previously discovered in patients and murine models that higher levels of pro-inflammatory signals before stem cell infusion are associated with the severity of aGVHD. Here, we show that extracellular vesicles (EVs) mediate the intracellular delivery of SOCS3 (suppressor of cytokine signaling 3), resulting in reduced inflammatory signaling and macrophage/dendritic cell (DC) activation.

Furthermore, single-dose treatment with engineered SOCS3-loaded EVs (eEVs) significantly prevented aGVHD and increased survival in multiple murine models without compromising graft-versus-leukemia activity. Mechanistically, single-cell transcriptomics revealed that eEVs induced transcriptional features associated with an immunoregulatory milieu in recipients before allo-HSCT, and then suppressed excessive immune responses, resulting in aGVHD alleviation.