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Oscillating magnetic fields (OMF) produced by a new device with rotating magnets produces rapid apoptosis of patient derived glioblastoma (GBM) cells in culture. We have proposed that this is due to a sequence of events triggered by the well-established mT-range magnetic influence on the radical electron pair mechanism in the mitochondrial respiratory electron transport chain (ETC). Here we present results of preclinical studies in support of this mitochondrial hypothesis, accounting for the oncolytic effects of OMF. We tested a range of in vitro treatment protocols, involving changes in frequency and timing of OMF, to arrive at an optimally effective set of parameters. After hours of exposure to this optimized intermittent pattern of OMF killed not only patient derived GBM cells, but cells of 4 other malignant tumors in a cell culture dish. This treatment was not lethal to normal human astrocytes, bronchial epithelial cells, and B lymphocytes. Exposure to static magnetic fields and continuous OMF did not produce any oncolysis. The oncolytic effect of OMF was potentiated by compounds that enhance mitochondrial metabolism, e.g. β-hydroxybutyrate. The underlying cellular mechanism of OMF action involved complete arrest of ETC-dependent consumption of oxygen, accelerated upregulation of the levels of reactive oxygen species, opening of the mitochondrial membrane permeability transition pore, and disruption of the mitochondrial network, leading to caspase-dependent apoptosis of cancer cells. Daily treatment in a late-stage mouse model consisting of human GBM xenografts implanted into the brains of immunocompromised mice produced significant survival benefit. These findings document the potent oncolytic effects of OMF and specific mechanisms of action that will likely provide a novel and powerful treatment against GBM and a wide range of other solid malignant tumors. Clinical trials of this therapy are underway at our institution.

EXTH-13. POTENT ANTICANCER EFFECTS OF A NEW WEARABLE NONINVASIVE ONCOMAGNETIC DEVICE: CELLULAR MECHANISMS OF ACTION