Intratumoral delivery of interleukin 12 expression plasmids with in vivo electroporation is effective for colon and renal cancer

We report on an antitumor treatment involving electrogene therapy (EGT), a newly developed in vivo gene transfer method using electroporation. We carr ied out in vivo EGT in a subcutaneous model of CT26 colon carcinoma cells, using plasmid DNAs encoding interleukin 12 (IL-12) subunits. For this purpo se, we developed two IL-12 expression systems: a cotransfer system using a plasmid encoding the IL-12 p40 subunit and a plasmid encoding the IL-12 p35 subunit, and a single-vector system using a plasmid expressing a p40-p35 f usion protein. Both transfer systems significantly inhibited the growth of CT26 tumor. Immunohistochemical analysis of IL-12 EGT-treated tumors reveal ed enhanced infiltration of CD8(+) cells into the tumor tissue, while rever se transcriptase-polymerase chain reaction confirmed the increased expressi on of interferon gamma within treated tumors. The same IL-12 EGT applied to the nude mouse model was not effective, suggesting the critical role of T cell infiltration in this treatment. The inhibitory effects revealed in exp eriments in which previously treated mice were rechallenged with a second i noculation of CT26 tumor cells suggested that IL-12 EGT may also establish partial systemic antitumor immunity. The growth of IL-12 EGT-treated Renca tumors, a renal cell carcinoma, was also significantly inhibited. These fin dings suggest that EGT of the IL-12 gene has the potential to be an effecti ve anticancer gene therapy.