A non-viral gene therapy for melanoma by staphylococcal enterotoxin A

Staphylococcal enterotoxin A (SEA) derived from Staphylococcus aureus , as a superantigen, shows potential for cancer immunotherapy, but systemic immunotoxicity restricts its clinical application. Targeted delivery of SEA to tumor site provides a promising option for reducing the systemic toxicity. Here, we constructed an iRGD peptide (H-[Cys-Arg-Gly-Asp-Lys-Gly-Pro-Asp-Cys]-NH2 ) modified nanoparticle (iDPP) to deliver plasmids encoding SEA for melanoma treatment. The iDPP/SEA nanocomplexes efficiently mediated SEA expression in B16-F10 cells in vivo and in vitro and induced the activation of lymphocytes and maturation of murine bone marrow-derived dendritic cells (BMDCs) in vitro . In the subcutaneous B16-F10 melanoma model, the iDPP/SEA nanocomplexes could effectively enhance immune response and T lymphocytes infiltration in tumor site after intravenous administration, thereby considerably decreased melanoma growth. Meanwhile, no obvious adverse effect was observed after intravenous administration of the iDPP/SEA nanocomplexes in vivo . Our findings demonstrated that gene therapy of SEA is a potential candidate for melanoma treatment. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.