Tumor Treating Fields (TTFields) are an antineoplastic treatment modality that target dividing cancer cells and are delivered continuously to the patient, using a portable signal generator and 2 pairs of transducers arrays attached to the skin. FDA approval was received for glioblastoma (GBM) and malignant pleural mesothelioma (MPM) treatment, following clinical trials demonstrating the safety and efficacy of TTFields. While in vitro research tools for TTFields are now available, in vivo experiments were so far limited due to the lack of a dedicated animal delivery system that allows for continuous TTFields application. The main challenge associated with continuous TTFields delivery to mouse models are an absolute requirement for adequate and continuous contact between array electrodes and skin throughout treatment. Another challenge is the need to deliver the electric fields through multiple wired conductors connected to electrodes, thus limiting movement and imposing stress on the animal. This work aimed to develop an in vivo system that allows for continuous, 2 direction delivery of TTFields to mice bearing cancer tumors in the torso or flank for the duration of 1 week and to address challenges.
To overcome limitations and to develop a viable in vivo system, the following approaches were tested: 1) evaluation of various electrode layouts for optimal TTFields delivery to orthotopic torso and subcutaneous flank tumors; 2) examination of different adhesive materials and designs to ensure proper skin adherence; and 3) assessment of various solutions to prevent wire entanglement.
The final design of the transducer array electrodes included 2 different adhesive layers. The adhesives consisted of a more delicate, flexible inner layer to improve skin adherence without harming the mice and a breathable, durable, non-woven outer layer to secure skin electrodes. Multiple conductors were compacted into a single flat, flexible, lightweight printed circuit cable. The system design also included a novel electric swivel machine that prevents the cable from coiling, by sensing animal movement and rotating in accordance. To further reduce the impact of stress factors on the mice during TTFields treatment, a cage that houses 2 mice separately yet providing mice with the opportunity to interact was developed. This in vivo method was modeled to reduce stress on mice and has shown diminished reductions in weight loss throughout the course of treatment.
The new inovivo system will provide researchers with a comprehensive tool to conduct TTFields experiments in mice; and to further elucidate the effects of TTFields on the whole animal and specifically on the tumor microenvironment and immune system. This devised inovivo tool provides means for continuous, 2 direction TTFields delivery to tumors in the torso or flank for the duration of 1 week with minimal stress on the mice.
Citation Format: Shiri Davidi, Roni Blat, Anna Shteingauz, Sara Gerstein, Yaara Porat, Moshe Giladi, Uri Weinberg, Yoram Palti. The inovivo system: A novel in vivo tool for the application of Tumor Treating Fields (TTFields) to mice [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2740.