IMMU-31. Investigating innate immune targeting of pediatric high grade glioma via STING immunostimulation and therapeutic anti-tumor antibodies

Abstract At present, there is a lack of effective treatments for pediatric high-grade glioma (pHGG). While conventional immunotherapies have been effective in treating cancers outside the central nervous system (CNS), they have been largely unsuccessful in CNS malignancies. Research conducted primarily on adult brain tumors has demonstrated the importance of immunoediting and the tumor microenvironment (TME) in both preventing disease progression and facilitating tumor escape. Building on this understanding, our research aims to explore the interactions of pHGG with the innate immune system, with the goal of harnessing anti-tumor activity through immunotherapy. The growing body of knowledge about pHGG highlights important differences compared to adult glioblastoma (GBM), extending beyond genomic mutational profiles. In this study, we investigated the expression of the immunostimulatory STING signaling pathway in pHGG cells, as well as the immunological target GD2 ganglioside. We demonstrate that STING pathway components are expressed in pHGG cells and that treatment with the STING agonist ADU-S100 induces robust downstream signaling, resulting in type I interferon secretion and increased cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays. Furthermore, our research demonstrates strong expression of GD2 in pHGG cell lines. Delivery of the anti-GD2 monoclonal antibody Dinutuximab to these tumors activates the anti-tumor effects of PBMCs. Lastly, we explore tumor modulation of the GD2 target when undergoing immune stress. These findings highlight promising therapeutic approaches for pHGG, emphasizing the potential of targeted immunotherapies and increasing our understanding of tumor response to immune pressure.