3064 - Reducing Fibrosis with Tumor Treating Fields

05:00pm - 06:00pm PT

Hall F

Screen: 19

POSTER

Presenter(s)

Emma Higgins, BS - Franciscan University of Steubenville, Steubenville, OH

E. Higgins¹, J. Reitemeyer¹, B. Bartosik¹, C. Reohr¹, J. A. Pathakamuri¹, D. Kuebler¹, J. R. Henderson², and J. J. O'Connell^3,4; ¹Franciscan University of Steubenville, Steubenville, OH, ²Quiverent LLC, Greenville, SC, ³Prisma Health Cancer Institute, Greenville, SC, ⁴University of South Carolina School of Medicine Greenville, Greenville, SC

Purpose/Objective(s): We hypothesize that the dielectric force induced by Tumor-Treating Fields (TTF) on Septins involved in microtubule assembly, causing mitotic catastrophe, may also cause disorder in collagen organization in the extracellular matrix during fibrosis. Both processes share common Septin complexes, and biochemical spindle poisons such as paclitaxel can mitigate tissue fibrosis by suppressing the TGF-ß1/Smad3 signaling pathway. Our primary objective was to assess whether a biophysical spindle poison that can be applied on target and controlled at will, could also mitigate a fibrotic response to tissue injury.

Materials/Methods: We developed and validated a custom-built system that delivers a wide variety of TTF, allowing for arbitrary waveforms to include frequency-modulated TTF (FM-TTF). Because TGF-ß1 appears to have a causative role in the development of radiation-induced fibrosis (RIF) by activation of TGF-ß1 signaling pathways, our study used the administration of TGF-ß as an in vitro surrogate for exposure to ionizing radiation. Confluent primary human adipose-derived mesenchymal stem cells (MSCs) were treated with 10 ng/mL TGF-ß and 50 ug/mL ascorbic acid to promote fibroblast differentiation and collagen deposition

After 24 hours, fibroblasts and undifferentiated mesenchymal stem cells (MSCs) were cultured for 7 days under identical conditions. One group was exposed to Frequency-Modulated Tumor-Treating Fields (FM-TTF) and the other served as a control without FM-TTF exposure. FM-TTF were delivered with a field strength of 1.2 V_RMS/cm at a frequency of 150 kHz modulated over a range of ±10 kHz. Frequency was modulated with a Triangle waveform at a frequency of 16.7 mHz. After the culture period, collagen was quantified using Sirius red dye staining. The collagen quantification data was compared between the FM-TTF-exposed and control groups.

Results: Our results show that in the presence of TGF-ß and ascorbic acid, MSCs successfully differentiated and produced collagen compared to the undifferentiated MSCs. When FM-TTF were applied to the differentiated MSCs, collagen secretion was reduced approximately by 50% compared to the differentiated control without FM-TTF. In the undifferentiated MSCs, there was no significant difference in collagen measurements between the cells treated with FM-TTF and the untreated cells.

Conclusion: These results suggest that TTF reduces collagen secretion and, thereby, fibrosis in human fibroblasts. Since RIF is often a dose-limiting toxicity causing normal tissue complications in standard courses of radiation treatments, we recommend further research of TTF to reduce the effects of RIF and tissue fibrosis more broadly. We aim to extend these findings to in vivo models and clinical settings to evaluate the efficacy of TTF in reducing RIF.

Abstract 3064 - Table 1

	FM-TTF	Control
	Measured Collagen (Absorbance at 550 nm)
Undifferentiated MSCs	0.439	0.385
Differentiated Fibroblasts	0.430	0.821