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.