Projects / Programmes
Development and evaluation of new approaches to cancer treatment
January 1, 2015
- December 31, 2021
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B200 |
Biomedical sciences |
Cytology, oncology, cancerology |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
Biomedical applications of electroporation; gene therapy; radiosensitization; clinical trials, humans, veterinary
Researchers (37)
Organisations (2)
Abstract
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. It is a translational program, which will encompass both, preclinical and clinical research.
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 and stem cells. 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 vascular-targeting and immunomodulating 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 evaluated first in veterinary oncology, as the best approach for the translation into the human 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, pancreatic and mammary tumors. The developments in gene electrotransfer to tumors will be evaluated in human clinical trials as well.
The program is interdisciplinary; it will be executed in close collaboration between the researchers and clinicians, within the research community in Slovenia, as well as in collaboration with international partners. Most of the equipment is already available; from molecular laboratory, to cell laboratory, irradiation facility, animal colony and clinical environment. The vast experience that was gained so far in this research area is the guarantee for successful continuance of our program.
Significance for science
The proposed research program is continuation of the previous one. Its goal is to promote and develop electroporation based medical applications in the field of electrochemotherapy and gene therapy. Additionally, we will investigate and develop new systems for gene delivery, cold plasma for skin delivery and mesenchymal stem cells for specific tumor targeting.
Electrochemotherapy is a non-thermal ablation technique that has spread now into more than 135 centers throughout the Europe. Our group, as pioneers in this field, has helped to develop its applications in treatment of cutaneous tumors, but now we are translating this technology into treatment of deep seated tumors. Also in this field we have been the pioneers, publishing the first clinical study, on 16 patients with liver metastases, and demonstrated safety and efficacy of the treatment. With further development in this field, our contribution in translating electrochemotherapy into treatment of other deep seated tumors will bring great contribution for the application of this technology in treatment of cancer.
Gene therapy is innovative and rapidly growing treatment approach for cancer. Gene electrotransfer has been now recognized to have potential as delivery system, predominantly because of its safety compared to viral vectors. We are already developing plasmids encoding therapeutic molecules that would give antiangiogenic or immunomodulatory effectiveness. By further development and evaluation of the effectiveness we will foster this treatment approach into translational research, especially if it proves to be feasible and effective in combined treatment with radiation therapy. We have already been involved in one gene therapy trial, using plasmid AMEP, as one of the first gene therapy trials using gene electrotransfer, but will proceed with our efforts to prepare new plasmids for translation into the clinics, or get involved in international trials. This activity would certainly have great impact in the role of gene therapy in cancer treatment.
Both electrochemotherapy and gene electrotransfer will be translated into veterinary oncology, where we have been the leading actors so far, and intend to continue so. The implementation of this simple technology into veterinary oncology is specifically important for wellbeing of animals, but the experience gained is very useful and sets the stage for translation into human oncology.
Furthermore, we will focus our research also on new delivery systems for gene therapy. We will investigate cold plasma, which is very suitable for delivery of therapeutic molecules to skin enabling treatment of accessible skin tumors and DNA vaccination. Additionally, to target deeper seated tumors, we will use mesenchymal stem cell that will be ex vivo loaded with the selected therapeutic plasmids using our established method electroporation.
Significance for the country
Cancer incidence is steadily increasing, and the treatment of cancer patients is a growing financial burden for national health security systems. Specifically, because new targeted therapies are costly, however their effectiveness is below expectation. The impact of new therapeutic approach on health care system costs is an important factor in providing not only efficient but also less resource-intensive treatment approaches.
With development of new therapeutic approaches, we would add to armamentarium a new therapy that would be based on electroporation based technologies. The technology is relatively cheap and is applicable for drugs (electrochemotherapy) or genes (gene electrotransfer). By its development it could replace other more costly treatments.
For development of such therapeutic approach collaboration between academia and industrial partners is necessary. Regarding this program, IGEA is an industrial partner with experience in development of most advanced medical devices for implementation of electroporation-based treatments in the clinics. In this project, new technical developments will be sought and implemented, and consequently provided for the broader clinical use.
The development of treatment planning for ECT in deep-seated tumors will provide a platform for its safe and accurate use, not only in treatment of liver but also other deep-seated tumors.
New knowledge will be carefully monitored and if patentable, patent applications will be prepared, filed and contacts established with potentially interested users. Intellectual property will be protected according to the terms of participating institutions.
Indirect impact of this project for society will be the inclusion of the project in postgraduate studies in Slovenia as well as on the international level. According to this, doctoral students will be involved into the project and the results will be implemented in their doctoral thesis.
Furthermore, the results obtained from this project will be presented at international conferences, summer schools and in the form of peer-reviewed publications, which will contribute to the international promotion of Slovenia as a prosperous country with a society of innovative and modern medical approaches.
Most important scientific results
Annual report
2015,
interim report
Most important socioeconomically and culturally relevant results
Annual report
2015,
interim report
