Abstract 7513: Tumor treating fields (TTFields) can induce immunogenic cell death in GBM resulting in enhanced immune modulation

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Abstract Glioblastoma (GBM) is the most common and aggressive form of malignant primary brain tumors. Despite current standard of care, the overall survival for GBM is ~15 months. While immunotherapy using immune checkpoint inhibitors such as anti-PD-1/PD-L1 have been efficacious for solid malignancies, very little progress has been made in a clinical setting for GBM. This is mainly due to GBM being known as a “cold” and non-immunogenic tumor. It has been previously established that a tumor may become “hot” if the T cell responses can be enhanced by increasing the presentation of tumor-specific antigens to the immune system. Tumor Treating Fields (TTFields) are alternating electric fields in a specific frequency range (100-500 kHz) delivered to the human body through transducer arrays. Treatment with TTFields have been approved and have shown efficacy in GBM. TTFields have induced immunogenic cell death in GBM, which in turn can elicit anti-tumoral immunity by inducing damage-associated molecular patterns (DAMP). These patterns are important for promoting engulfment of lung cancer cells by dendritic cells and recruitment of immune cells. These findings suggest that TTFields may enhance the immune response in GBM by increasing tumor specific antigens. In this study we show in vitro that TTFields enhanced the immune response to GBM. We initially demonstrated that GBM cells (GL261 or CT2A) treated with TTFields (200 kHz) can elicit DAMP emissions as evident by the increase in secretion of ATP and HMGB1 and the enhanced translocation of calreticulin to the cell surface. Additionally, TTFields stimulated the phagocytotic activity of antigen presenting cells (Raw264.7) and increased T-cell early activation (CD69/CD4+, CD69/CD8+) and activity (IFNγ and perforin). Since our findings in vitro indicate TTFields enhanced the immune response to GBM, we studied the therapeutic potential of using TTFields together with anti- PD1 in a syngeneic mouse model. We applied TTFields to GBM cells prior to intracranial injections. While our survival studies are preliminary, our findings suggest that systemic anti-PD1 and TTFields may result in a myeloid and T-cell mediated anti-tumor response and enhanced survival. Our findings indicate that TTFields treatment may help transform GBM into a “hot” tumor thereby making it an attractive target for immunotherapy. Citation Format: Ryan T. Nitta, Si Yeon Lee, Michael Lim, Gordon Li. Tumor treating fields (TTFields) can induce immunogenic cell death in GBM resulting in enhanced immune modulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7513.