Development and evaluation of new approaches to cancer treatment

Our research is aimed at development and evaluation of new, innovative approaches in cancer treatment. It is conducted predominantly at the Department of Experimental Oncology at the Institute of Oncology Ljubljana, with close cooperation with the clinical departments in our institution, the University of Primorska and research community of Slovenia. It is a translational program, which will encompass both, preclinical and clinical research. Close collaboration of researchers and clinicians make this research programme highly interdisciplinary. Many activities will be conducted also with international partners, in Europe as well as in U.S.A.. In preclinical level we will focus on electroporation based drug (electrochemotherapy) and gene delivery, as well as on other means of delivery, such as cold plasma. Systems for gene delivery and therapy to various tissues and tumors will be developed, their mechanisms of action explored, and evaluated in preclinical models in vitro and in vivo for possible translation into the clinics. We will concentrate on immunomodulating and vascular-targeting gene therapy approaches and explore their value in combination with irradiation, as these approaches can act as radiosensitizers. Radiosensitizing effects of combined therapy approach will be tested in preclinical level, in mouse tumor models, and the underlying mechanisms of action explored. The clinical application of the developed approaches, as well as of electrochemotherapy, will be implemented and tested in veterinary oncology, as the best approach for the translation into the human clinical oncology. In clinical studies we will perform the treatment of tumors in cats and dogs, patients referred to the Clinic for Surgery and Small Animals at the Veterinary Faculty of University of Ljubljana. The gained experience will be applied in the human clinical trials in our own institution, or in collaboration with other clinical institutions in Ljubljana, or international partners. Foreseen are the clinical trials in electrochemotherapy, both, for cutaneous and deep seated tumors, like primary liver tumors and liver metastases and pancreatic tumors. The developments in gene electrotransfer to tumors will be evaluated in human clinical trials as well. The goal is to translate gene electrotransfer of plasmids into treatment of skin tumors as the only treatment or in combination with other local ablative therapies, such as radiation therapy or electrochemotherapy. In summary, the research programme is structured in a way to translate the innovative treatment approaches like electrochemotherapy and gene electrotransfer from bench to bedside.

Our translational approach will strive to develop and implement new treatment options for the treament of cancer. In preclinical level we will focus on electroporation based drug (electrochemotherapy) and gene delivery, as well as on other means of delivery, such as cold plasma. Systems for gene delivery and therapy to various tissues and tumors will be developed, their mechanisms of action explored, and evaluated in preclinical models in vitro and in vivo for possible translation into the clinics. We will concentrate on immunomodulating and vascular-targeting gene therapy approaches and explore their value in combination with irradiation, as these approaches can act as radiosensitizers. Radiosensitizing effects of combined therapy approach will be tested in preclinical level, in mouse tumor models, and the underlying mechanisms of action explored. The clinical application of the developed approaches, as well as of electrochemotherapy, will be implemented and tested in veterinary oncology, as the best approach for the translation into the human clinical oncology. The gained experience will be applied in the human clinical trials. Foreseen are the clinical trials in electrochemotherapy, both, for cutaneous and deep seated tumors, like primary liver tumors and liver metastases and pancreatic tumors. The developments in gene electrotransfer to tumors will be evaluated in human clinical trials as well. The goal is to translate gene electrotransfer of plasmids into treatment of skin tumors .In summary, the research programme is structured in a way to translate the innovative treatment approaches like electrochemotherapy and gene electrotransfer from bench to bedside.

Our programme grant has a strong translational potential that bridges basic and applied preclinical studies with the clinical practice in human and veterinary oncology. The research has potential to bring new treatment to the clinics and have benefit to the cancer patients. Namenly, we succesfully developed electrochemotherapy from bench to bedside. Our translational approach has proved very successful in the case of translation of electrochemotherapy from investigations of the effectiveness of electrochemotherapy on preclinical level and elucidating its mechanisms of action into clinical applications. We will continue to develop new clinical apllications of electrochemotherapy in several clinical studies as well as seek for potental treatment combinations. Our next goal is also to implement gene therapy for the treatment of cancer in Slovenia. For this purpose, we developed a new drug product, plasmid encoding interleukin 12, whic will be in the next years tested in first-in-human phase I clinical study and if proved safe, confirmitory and combination clinical studies will be done.