Supercharged eGFP-TRAIL Decorated NETs to Ensnare and Kill Disseminated Tumor Cells

BACKGROUND: NETosis is an innate immune response elicited by activated neutrophils to fight microbial infections. Activated neutrophils release DNA fibers decorated with anti-microbial proteins called neutrophil extracellular traps (NETs) into the extracellular space to trap and kill surrounding microbes. METHODS: Here, we show that tumor-derived IL-8 released by cancer cells also activates the release of NETs. Until now, there have been no existing technologies that leverage NETs as an anti-tumor drug delivery vehicle. In this study, we demonstrate the re-engineering of neutrophils to express an apoptosis-inducing chimeric protein, supercharged eGFP-TRAIL, on NETs that can ensnare and kill tumor cells while retaining their anti-microbial capabilities. RESULTS: We observed significant TRAIL-induced apoptosis in tumor cells captured by TRAIL-decorated NETs. CONCLUSIONS: This work demonstrates NETs as a promising technology to deliver protein in response to local cytokine signals.