Abstract:
Background: Hyperthermia in oncology is a tool of destroying the malignant cells on thermal way. The action could be a direct thermal toxicity for cells and/or boost other therapies to eliminate cancer cells. The definite aim of curative hyperthermia is to be selective on the malignant cells. The tumor has a complex structure, contains various compartments from where the therapy have to select the targets. Furthermore, the malignancy is systemic; metastases appear. The task is to extend the local thermal effect to systemic. Our objective is to show how the selection and systematization could be managed by hyperthermia from bench to bedside; targeting the abscopal effects induced by local treatment.
Method: The method, which we had introduced is a modulated radiofrequency (RF) electro-hyperthermia treatment (mEHT, trade name: oncothermia). This technology is impedance controlled capacitive coupling with amplitude modulated 13.56 MHz carrier frequency by the time-fractal pattern. mEHT selectively targets the transmembrane protein clusters of malignant cells. The group of these transmembrane proteins is naturally built-up nanoparticles in the membranes of malignant-cells by definitely expressed lipid rafts.The nano-heating of rafts is thermal effect without direct heating of the mass of the tumor. It is measured that the rafts’ temperature is at least 3°C higher than the lipids around it.
Results: mEHT induced massive apoptotic cell death in the treated tumors by caspase independent subroutine in HT29 colorectal adenocarcinoma xenografts. This programmed cell death producesdamage associated molecular pattern which is a prerequisite of the immunogenic cell-death. The abscopal effect was measured in murine model in conjunction with intratumoral dendritic cell (DC) injection. The mEHT plus DC administration significantly inhibits the tumor growth, while even no re-challenging of the tumor was possible. In this case the abscopal effect works like vaccination. The mEHT method is successfully applied in many clinics, having some running and finished clinical studies for gliomas for hepatocellular carcinoma, for colorectal liver metastasis for lung and for numerous others. Conclusion: mEHT induces tumor cell apoptosis and creates favorable tumor microenvironment for tumor specific immunological chain reaction. It is directly applied curatively in numerous hospitals and clinics.
