RDNA-07. IDH1-MUTANT GLIOBLASTOMA (GBM) CELLS FROM A PATIENT POST-TUMOR TREATING FIELDS (TTFIELDS) THERAPY ARE SENSITIVE TO TTFIELDS IN VITRO

Abstract

BACKGROUND: Tumor treating fields (TTFields) are FDA-approved for treatment of newly-diagnosed and recurrent GBM. TTFields extend progression-free survival and overall survival. Despite this advancement in patient outcome, many patients undergoing TTFields treatment ultimately progress with tumor recurrence. In this study, cell lines were generated from resected GBMs from two patients with secondary isocitrate dehydrogenase 1 (IDH1)-mutant glioblastoma. One patient received TTFields monotherapy for 1 year prior to resection, and one patient was TTFields-naïve. Cells were treated in vitro with TTFields followed by assessment of proliferative activity and cytotoxicity. METHODS: Tumors were enzymatically and mechanically disrupted to generate single-cell suspensions for culturing. Cells grew in DMEM/F12 media with 10% fetal bovine serum and gentamicin. Prior to TTFields application, cells were plated on plastic coverslips (2×104cells/coverslip) and incubated overnight. Then, TTFields were applied at 200 kHz (field intensity ∼1.6 V/cm) for 14 days. Proliferation and cytotoxicity were assessed with XTT assay (n=6/group) and lactate dehydrogenase (LDH) release assay (n=3/group), respectively. Groups were compared by one-tailed t-test. RESULTS: After 14 days, proliferation was reduced in TTFields-treated cells (mean±SD; 0.763±0.075) compared to control cells (1.064±0.014; p<0.002) in the cells from the TTFields-treated patient, with no significant difference between groups in the cells from the TTFields-naïve patient (treated 1.269±0.064; control 1.184±0.097). However, in both cell lines, in vitro TTFields increased LDH release. In cells from the TTFields naïve patient, LDH release increased (12.62±0.96) compared to control (7.375±0.98; p<0.002). In the TTFields-treated patient cells, LDH release was 3-fold greater than control (31.890±16.7 vs. 9.001±1.21; p<0.04). CONCLUSION: TTFields decreased proliferation and induced cytotoxicity in IDH1-mutant GBM cells in vitro. This is the first report of in vitro effects of TTFields on GBM cells with mutated IDH1.