Author/Editor		Kamenšek, Urška; Čemažar, Maja; Lampreht Tratar, Urša; Uršič, Katja; Serša, Gregor
Title		Antitumor in situ vaccination effect of TNF[alfa] and IL-12 plasmid DNA electrotransfer in a murine melanoma model
Type		članek
Vol. and No.		Letnik 67, št. 5
Publication year		2018
Volume		str. str. 785-795
ISSN		0340-7004 - Cancer immunology, immunotherapy : CII
Language		eng
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 (TNF%), 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 TNF% 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 and effective in eliciting a potent and durable antitumor response; therefore, further studies of this approach are warranted.
Keywords		elektroprenos genov interlevkin 12 melanom glodalci gene electroporation interleukin 12 melanoma murine