TMIC-10. Analyzing Tumor Treating Fields (TTFields) therapy concomitantly with checkpoint inhibitors in a GBM mouse model

Glioblastoma (GBM) is the most common malignant form of adult brain tumor, with a median survival of around 1.5-2 years. Despite multimodal treatments (tumor resection, radiotherapy, and chemotherapy) achieving an effective cure remains a significant challenge due to its highly aggressive nature. Immune checkpoint inhibitors have emerged as a promising strategy to combat GBM; however, limitations have hindered clinical success, largely due to the “cold” and immunosuppressive tumor microenvironment (TME). Tumor Treating Fields (TTFields) are a non-invasive, FDA approved treatment for GBM that employs specific frequency ranges (100-500 kHz) delivered loco-regionally transducer arrays placed on the head. In our present study, we studied the effects of TTFields treatments on the immune response by using a syngeneic murine glioma model. Our initial in vitro studies confirmed that TTFields enhanced the immune response in GBM by inducing immunogenic cell death, which led to the recruitment of immune cells through the release of damage-associated molecular patterns (DAMPs). Additionally, we demonstrated that TTFields increased T-cell activity (IFNγ and perforin) and enhanced the motility and phagocytic activity in antigen presenting cells (Raw 264.7) and dendritic cells (JawsII). We then studied the therapeutic potential using the inovivo system to directly apply TTFields (200kHz) to a subcutaneous syngeneic GBM mouse model (CT2A-luciferase) concomitantly with the checkpoint inhibitor anti PD-1. Consistent with previous findings, the single arm treatments of TTFields and anti PD-1 reduced tumor volume and slightly modulated the immune environment. Concomitant treatment of TTFields with systemic anti PD-1 therapy reduced tumor volume and significantly increased immunomodulation, as observed via an increase in helper T-cells (CD4), cytotoxic T-cells (CD8), macrophages (CD11b) and dendritic cells (CD11c). Our findings suggest that concomitant treatment of TTFields with checkpoint inhibitors has the potential to help transform GBM into a “hot” tumor, making it an attractive target for immunotherapy.