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Article Abstract
Treatment with mRNA-based therapeutics represents a potential strategy for improving outcomes of diverse diseases. Tumor-specific toxins might represent ideal candidates for mRNA-based cancer therapeutics. Here, we investigated the anti-tumor potential of lipid nanoparticle (LNP)-encapsulated mRNA encoding the tumor-specific toxin protein neutrophil elastase (ELANE or PPE). Treatment of either ELANE or PPE mRNA-LNP selectively killed various cancer cell types but not non-cancer cells in vitro. Furthermore, ELANE and PPE mRNA-LNP administration significantly inhibited tumor growth in vivo and induced CD8+ T cell infiltration, while no acute toxicity was observed in mice. Several additional elastases from different species were also effective against cancer cells. Altogether, these data support further development of tumor-specific toxin protein mRNA-LNP as a therapeutic strategy for cancer.
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| http://dx.doi.org/10.1158/0008-5472.CAN-24-3914 | DOI Listing |
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