Electroporation for improving the quality of life
When a cell is exposed to an electric field of sufficient amplitude its membrane becomes permeable for molecules that otherwise are deprived of transmembrane transport mechanisms. Some chemotherapeutic drugs which have intracellular target but lack efficient transport across the membrane (e.g. bleomycin, cisplatin) can greatly benefit from membrane permeabilization (electroporation). Bleomycin cytotoxicity has been demonstrated to be increased 1.000-10.000 times, whereas for cisplatin this potentiation in vitro was 10-100 times. This potentiation of drug cytotoxicity was effectively translated from in vitro to in vivo preclinical trials and finally introduced into clinical practice as electrochemotherapy. The metastases of different origin have responded locally to electrochemotherapy with overall complete response rate of 59.4% and objective response rate of 84.1%. Since 2006, electrochemotherapy has been introduced into more than 150 clinical centers around Europe and is paving its way into standard clinical use. The procedure is efficient, safe, well tolerated by patients and can be performed on an outpatient basis.
As electroporation of membranes of cells in tissue depends predominantly on local electric field, it is possible to treat with electrochemotherapy also internal tumors. Local electric field can be established by inserting electrodes into the tissue. The “shaping” of the field by using multiple electrodes in combination with treatment planning procedures and image guided insertion of electrodes allows treating of solid tumors irrespective of their location. Recent clinical trials in treating colorectal liver metastasis, metastasis in bone, and soft tissue sarcoma by means of needle electrodes proved feasibility of electrochemotherapy for deep seated tumors making this new treatment modality a promising new tool in armamentarium of oncologists.
In a similar fashion electroporation can be used to introduce large molecules like pDNA both in vitro as well as in vivo which is used for gene therapy and DNA vaccination. Electroporation of cells can however also lead to cell death, which has been recognized as non-thermal ablation method of soft tissue and has already be demonstrated for its use in clinical setting for tumor ablation and myocardial ablation in animal model.
Biography
Damijan Miklavčič received a Ph.D. in Electrical Engineering from the University of Ljubljana in 1993. He is Full Professor and Head of the Laboratory of Biocybernetics at the Faculty of Electrical Engineering, University of Ljubljana, where he previously served also as vice-dean for research and Chair of the Department of Biomedical Engineering.
Throughout his academic career he has been active in rehabilitation engineering, experimental oncology, and cell biology. In the last two decades he specifically focused on electroporation‐based gene transfer and drug delivery coupled with theoretical modeling of biophysical and biological processes, as well as development of hardware allowing for efficient electroporation both in vitro and in vivo. His current interests lie in further advancing electrochemotherapy as local treatment of internal malignant tumors, transferring the knowledge on tissue electroporation to other fields like food science, and development of innovative environmentally-friendly applications of electroporation.
Damijan Miklavčič has lead a number of national and international research projects including a global network funded by COST (www.electroporation.net), and organized various international scientific meetings with one of most recent being the 1st World Congress on Electroporation. He has served as editor and guest editor in various scientific journals, and collaborated with more than 60 SCI journals as reviewer.