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Mediators of Inflammation
Volume 2017, Article ID 5285890, 11 pages
Research Article

Gene Electrotransfer of Plasmid-Encoding IL-12 Recruits the M1 Macrophages and Antigen-Presenting Cells Inducing the Eradication of Aggressive B16F10 Murine Melanoma

1Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, Ljubljana, Slovenia
2Laboratory of Genetic and Clinical Pathology, University Campus Bio-Medico of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy
3Laboratory of Oncology, IRCCS “Casa Sollievo della Sofferenza”, Viale dei Cappuccini, 71013 San Giovanni Rotondo, Italy
4Faculty of Health Sciences, University of Primorska, Polje 42, Izola, Slovenia
5National Research Council-Institute of Translational Pharmacology (CNR-IFT), Via Fosso del Cavaliere 100, Rome, Italy

Correspondence should be addressed to Maja Cemazar; is.i-okno@razamecm and Emanuela Signori; ti.rnc.tfi@irongis.aleuname

Received 9 January 2017; Revised 3 March 2017; Accepted 12 March 2017; Published 17 May 2017

Academic Editor: Rafael E. Marques

Copyright © 2017 Ursa Lampreht Tratar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Cancer immunotherapy is currently one of the leading approaches in cancer treatment. Gene electrotransfer of plasmids encoding interleukin 12 (IL-12) into the cells leads to the production of IL-12, which drives immune cell polarization to an antitumoral response. One of the cell types that shows great promise in targeting tumor cells under the influence of IL-12 cytokine milieu is that of macrophages. Therefore, the aim of this study was to evaluate gene electrotransfer of antibiotic resistance-free plasmid DNA-encoding murine IL-12 (mIL-12) in mice bearing aggressive B16F10 murine melanoma. IL-12 electrotransfer resulted in the complete long-term eradication of the tumors. Serum mIL-12 and murine interferon γ (mIFNγ) were increased after IL-12 gene electrotransfer. Further on, hematoxylin and eosin (HE) staining showed increased infiltration of immune cells that lasted from day 4 until day 14. Immunohistochemistry (IHC) staining of F4/80, MHCII, and CD11c showed higher positive staining in the IL-12 gene electrotransfer group than in the control groups. Immune cell infiltration into the tumors and the high density of MHCII- and CD11c-positive cells suggest an antitumor polarization of macrophages and the presence of antigen-presenting cells that contributes to the important antitumor effectiveness of IL-12.