Gene therapy in oncology, first steps of development in Slovenia

Gene therapy is also attracting interest in oncology. Probably the most interesting approach is immunostimulation. Plasmid DNA can be constructed, which is coding for a specific immunostimulatory molecule, which is then delivered into the cells, either in tumour or normal tissue. The transfected tissue then becomes the producer of the molecules encoded in the plasmid. The product is then released from the cells, either locally or systemically into the bloodstream. Since plasmids have hampered transport through the plasma membrane, delivery systems are needed that are either viral or nonviral. In our studies we predominantly use the non-viral transfection system, based on electroporation of the cells. Interleukin 12 (IL-12) is a cytokine with well-known anti-tumour and anti-angiogenic function. Therefore, in the SmartGene.si project we wanted to construct a plasmid DNA which is coding for IL-12 (plasmid phIL12), and perform all the necessary testing and prepare the documentation for its clinical testing in the treatment of skin tumours. The SmartGene.si consortium comprises partners from academia and industry. In the project it was necessary to prepare the plasmid according to the European Medicinal Agency (EMA) recommendations. For the application for the study approval submitted to the Agency for Medical Products and Medical Devices of the Republic of Slovenia (JAZMP), it was necessary to perform pharmacological, pharmacokinetic, and efficiency testing of phIL12. Thereafter, we had to develop the process and the facility, and prepare the drug. During the last three years, we have achieved all the goals and obtained the approval of the JAZMP for clinical testing of the product phIL12 in humans. We also obtained the approval of the National Ethics Committee. Currently, we are testing phIL-12 in a Phase I clinical protocol on head and neck skin tumours, with the aim to test the safety and feasibility of intratumoral gene electrotransfer of the plasmid phIL12. Another goal of the study is to determine a suitable dose of plasmid that could be used in future studies as adjuvant treatment to ablative therapies such as radiotherapy or electrochemotherapy.