Diffuse intrinsic pontine glioma cells are vulnerable to low intensity electric fields delivered by intratumoral modulation therapy

Abstract

Introduction Diffuse intrinsic pontine glioma (DIPG) is a high fatality pediatric brain cancer without effective treatment. The field of electrotherapeutics offers new potential for other forms of glioma but the efficacy of this strategy has not been reported for DIPG. This pilot study evaluated the susceptibility of patient-derived DIPG cells to low intensity electric fields delivered using a developing technology called intratumoral modulation therapy (IMT). Methods DIPG cells from autopsy specimens were treated with a custom-designed, in vitro IMT system. Computer-generated electric field simulation was performed to quantify IMT amplitude and distribution using continuous, low intensity, intermediate frequency stimulation parameters. Treatment groups included sham, IMT, temozolomide (TMZ) chemotherapy and radiation therapy (RT). The impact of single and multi-modality therapy was compared using spectrophotometric and flow cytometry viability analyses. Results DIPG cells exhibited robust, consistent susceptibility to IMT fields that significantly reduced cell viability compared to untreated control levels. The ratio of viable:non-viable DIPG cells transformed from ~ 6:1 in sham-treated to ~ 1.5:1 in IMT-treated conditions. The impact of IMT was similar to that of dual modality TMZ-RT therapy and the addition of IMT to this treatment combination dramatically reduced DIPG cell viability to ~ 20% of control values. Conclusions This proof-of-concept study provides a novel demonstration of marked DIPG cell susceptibility to low intensity electric fields delivered using IMT. The potent impact as a monotherapy and when integrated into multi-modality treatment platforms justifies further investigations into the potential of IMT as a critically needed biomedical innovation for DIPG.