Antitumor in situ vaccination effect of TNFα and IL-12 plasmid DNA electrotransfer in a murine melanoma model

Cancer Immunology, Immunotherapy : CII
Urska KamensekGregor Sersa

Abstract

Gene electrotransfer (GET) is one of the most efficient non-viral gene therapy approaches for the localized transfer of multiple genes into tumors in vivo; therefore, it is especially promising for delivering different cytokines that are toxic if administered systemically. In this study, we used concomitant intratumoral GET of two cytokines: tumor necrosis factor alpha (TNFα), a potent cytotoxic cytokine to induce in situ vaccination, and interleukin 12 (IL-12), an immunostimulatory cytokine to boost the primed local immune response into a systemic one. After performing GET in murine melanoma tumors, both TNFα and IL-12 mRNA levels were significantly increased, which resulted in a pronounced delay in tumor growth of 27 days and a prolonged survival time of mice. An antitumor immune response was confirmed by extensive infiltration of immune cells in the tumor site, and expansion of the effector immune cells in the sentinel lymph nodes. Furthermore, the effect of in situ vaccination was indicated by the presence of vitiligo localized to the treatment area and resistance of the mice to secondary challenge with tumor cells. Intratumoral GET of two cytokines, one for in situ vaccination and one for an immune boost, proved feasible a...Continue Reading

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Citations

Mar 11, 2020·Pharmaceutics·Catarina Roma-RodriguesAlexandra R Fernandes
Aug 9, 2020·Electromagnetic Biology and Medicine·C E Vera-TizatlA L Vera-Tizatl
Jan 9, 2019·Frontiers in Immunology·Hanne LocySarah K Maenhout
Jul 3, 2021·International Journal of Molecular Sciences·Alejandra G Martinez-PerezRoberto Montes-de-Oca-Luna

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Methods Mentioned

BETA
transfection

Software Mentioned

SigmaPlot
IDT Primer Quest
7300 System SDS

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