Abstract 5806: Analyzing tumor treating fields (TTFields) therapy combined with checkpoint inhibitors in a GBM mouse model

Abstract Glioblastoma (GBM) is the most common malignant form of adult brain tumor, with a median survival of around 15 months. 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). Previous studies have demonstrated that the TME can transform from “cold” to “hot” by upregulating tumor-specific antigens, thereby enhancing immune cell recognition. Tumor Treating Fields (TTFields) are a non-invasive treatment for solid tumors that employs specific frequency ranges (100-500 kHz) delivered through transducer arrays placed on the body. TTFields are currently being investigated for various tumor types and have received FDA approval and shown efficacy in GBM, pleural mesothelioma and metastatic NSCLC following platinum-based therapy. In our present study, we studied the effects of TTFields treatments on the immune response in GBM by using a syngeneic murine glioma model. Our initial in vitro studies demonstrated 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, co-culture experiments with splenocytes and GBM cells treated with TTFields showed an increase in activated dendritic cells and macrophages, as well as early activated T cells (CD69/CD4+, CD69/CD8+). We verified these findings by demonstrating 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). Since our in vitro findings indicated that TTFields enhanced the immune response, we studied the therapeutic potential of directly applying TTFields (200kHz) to a subcutaneous syngeneic GBM mouse model (GL261-luciferase) using the inovivo system. We observed a 2- to 4-fold decrease in tumor volume with mice that received TTFields treatment with the subcutaneous array compared to the control group (n = 8). In our subsequent studies, we anticipate that combining TTFields and the checkpoint inhibitor anti-PD-1 will result in greater tumor regression than TTFields monotherapy. Our findings suggest that concomitant treatment of TTFields with systemic anti PD-1 therapy has the potential to help transform GBM into a “hot” tumor, making it a more attractive target for immunotherapy. Citation Format: Si Yeon Lee, Caroline C. Perry, Kwang Bog Cho, Michael Lim, Gordon Li, Ryan T. Nitta. Analyzing tumor treating fields (TTFields) therapy combined with checkpoint inhibitors in a GBM mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5806.