EXTH-76. THE INOVIVO SYSTEM: A NOVEL PRECLINICAL TOOL FOR IN VIVO DELIVERY OF TUMOR TREATING FIELDS (TTFIELDS)

Abstract

Abstract Tumor Treating Fields (TTFields) are an antineoplastic treatment modality targeting dividing cancer cells, approved by the FDA for treatment of glioblastoma and malignant pleural mesothelioma. TTFields are delivered to the patient continuously, using a portable signal generator and 2 pairs of transducer arrays attached to the skin. While in vitro research tools for TTFields have been available, animal experiments were so far limited due to the lack of a dedicated TTFields in vivo delivery system. The main challenges associated with TTFields application to mice are the absolute requirement for adequate and continuous contact between array electrodes and animal skin throughout treatments; and the need to deliver the electric fields through multiple wired conductors connected to electrodes, which limit animal movement thus imposing stress. This work reports on development of an in vivo system to facilitate continuous delivery of TTFields to mice bearing cancer tumors in the torso or flank that addresses the aforementioned challenges. Three major developments were introduced to the system: 1) transducer array electrodes composed of delicate, flexible inner layer to improve skin adherence and a breathable, durable, outer layer to secure electrodes to the skin; 2) a novel electric swivel to prevent cable coiling; and 3) a cage constructed to house 2 mice separately while still allowing socializing. During a 1-week study, the new inovivo system demonstrated improvement compared to previous systems in the following areas: increased animal treatment compliance, less weight loss, and fewer number of array replacements. In conclusion, the new inovivo system is a comprehensive tool for continuous, 2 directional TTFields delivery to tumors in the torso or flank of mice for conducting TTFields experiments with minimal animal stress, thus allowing further elucidation of the effects of TTFields on the whole animal.