Abstract 337: Antitumor effect of oncomagnetic therapy in glioblastoma

Abstract Background: Glioblastoma (GBM) is the most lethal primary malignant brain tumor with a median survival of 15-20 months. Concurrent temozolomide (TMZ) chemotherapy and radiation (XRT) remain the current standard of care (SOC) treatment for newly diagnosed GBM. The addition of tumor treating fields (TTFs) improves median survival from 16 to 20.9 months. This modest improvement underscores the urgent need to identify a new treatment modality as standalone therapy. We have reported recently that brief 2 - 6 h of daily brain stimulation with a new noninvasive, non-contact, magnetic stimulation device causes >30% reduction of contrast-enhanced tumor (CET) volume in an end-stage recurrent GBM patient after a ~30-day treatment. Purpose: The noninvasive Oncomagnetic device developed in our laboratory selectively kills glioblastoma (GBM) and other cancer cells while sparing normal developing neurons and astrocytes in vitro. The spinning oscillating magnetic field (sOMF) generated by this device disrupts electron transport in the mitochondrial respiratory chain leading to a marked increase in reactive oxygen species (ROS) and consequent cancer cell death. However, the downstream molecular mechanism of sOMF action is under investigation. We studied the cellular and molecular effects of sOMF treatment on GBM cell lines and investigated the response to Oncomagnetic monotherapy (OMT) in a syngeneic mouse model. We treated LN229 and U87 GBM cells with sOMF with and without a sub-therapeutic dose of TMZ in vitro. To study the anticancer effect of sOMF in vivo, we developed syngeneic GBM tumors in BALB/c mice by stereotactic intracranial injection of GL261WT cells. Tumor growth was monitored periodically by MRI scans. Results: Our results showed that sOMF significantly reduce cell proliferation and cell survival in vitro. We observed that sOMF induces DNA damage and arrests cells in G1 phase of cell cycle. OMT of tumor-bearing mice using a whole-body sOMF stimulation method caused a substantial retardation of tumor growth and reduction of the contrast-enhanced tumor volume in 9.4 T MRI scans. OMT also showed significant increase in overall survival in these mice. Conclusion: These experiments contribute to unraveling the mechanism of action underlying the response to OMT in GBM and provide a strong rationale for a standalone Oncomagnetic therapy for GBM. Citation Format: Arvind Pandey, Shashank Hambarde, David S. Baskin, Santosh A. Helekar. Antitumor effect of oncomagnetic therapy in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 337.