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Electrogene therapy (EGT) with IL-12

STSM by Urša Lampreht, PhD Student

Period of mission: from 15/03/2015 to 31/05/2015

Home institution: Institute of Oncology Ljubljana, Ljubljana, Slovenia

Host institution: National Research Council (CNR), Institute of Translational Pharmacology, University Campus Bio- Medico of Rome, Rome, Italy

Gene electrotransfer (GET) is an effective method to introduce plasmids encoding different genes into cells. GET of plasmid encoding interleukin 12 (IL-12) already showed to have a good antitumor response resulting in significant tumor growth delay and tumor eradication. The mechanism of IL-12 is to elicit a strong immune response and to enhance the functioning of antigen presenting cells that infiltrate the tumors which leads to better recognition of tumor antigens and apoptosis of tumor cells. To visualize this characteristic of IL-12 the method of immunohistochemical staining is an excellent choice. Therefore the purpose of my STSM was evaluate immunohistochemically the involvement of antigen-presenting cells into the tumors following the  intratumoral GET of plasmid encoding IL-12. During STSM we have successfully optimized the protocol for the two antibodies F4/80 and MHCII.The obtained results showed that the electrogene therapy (GET) with both plasmid, therapeutic encoding IL-12 and control plasmid, induced the innate immune response, as there was a high infiltrate of macrophage in both samples regarding to the control group.To determine the M1 macrophages specific staining for MHCII was used. We observed a strong positive staining of cells expressing MHCII in the tumor samples which were treated with therapeutic plasmid. This kind of an observation was not seen in the group treated with control plasmid. Therefore, we can presume that the GET therapy with therapeutic plasmid encoding IL-12 induce the infiltration of M1 macrophages, which has antitumor activity that results in tumor growth delay and complete responses.


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