gms | German Medical Science

Objective: Tumor Treating Fields (TTFields) therapy is an CE certified anti-cancer treatment, delivered to patients continuously by 2 pairs of transducer arrays attached to the skin. In vivo TTFields studies were so far limited due to the lack of a dedicated animal delivery system. Two main challenges in this respect relate to ensuring: 1) adequate contact between arrays and the animal’s skin throughout the entire treatment; and 2) minimization of animal stress, due to motility limitations imposed by wires and individual housing needs (ie, to prevent wire entanglement from different mice). This work aimed to develop an in vivo system for continuous and effective TTFields delivery to mice.

Methods: To develop a viable system, several designs were tested: 1) various electrode layouts; 2) a variety of adhesive materials; 3) devices that prevent wire coiling; and 4) housing methods to reduce stress. Simulations were performed to ensure electric fields were generated at the desired locations.

Results: The final transducer array design for TTFields included 2 layers, an inner layer to improve adherence, and an outer layer to secure electrodes to the depilated skin. The conductors were compacted into a single printed circuit cable that connects to a novel electric swivel machine, which rotates in accordance to the animal’s movement to prevent cable coiling. Indeed, fewer cable entanglements occurred and fewer array replacements were needed, thus allowing for decreased need for animal handling and increased TTFields treatment compliance (continuity). A new cage was developed to allow pairs of mice to maintain dyadic social interactions during the experiment, while being housed separately. Indeed, animals treated with the inovivoTM system for 1 week displayed lower weight loss than animals treated with the previous non-dedicated system, indicative of reduced stress. In this initial tested torso orthotopic model, TTFields treatment was shown to generate above threshold intensities (>1 V/cm) in the lung, liver, pancreas, and other major organs, suggesting tumors in these torso organs may be treated effectively using the inovivo system.

Conclusion: The novel TTFields inovivo system provides means for continuous TTFields delivery to torsos of mice (while minimizing stress) to facilitate in vivo studies. The development of mouse head arrays to allow further research of TTFields for use in glioblastoma treatment (application of widespread interest) is currently underway.