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Abstract The tumor microenvironment (TME) consists of an enriched population of immune cells and milieu of factors that modulate key cellular processes such as angiogenesis, metabolism, apoptosis, migration, and proliferation. Previous studies have suggested that BPM 31510 induces ROS through high intra-cellular levels of ubidecarenone in aggressive cancer phenotypes both in vitro and in vivo through induction of mitochondrial ROS. Furthermore, we have previously observed efficacy of BPM 31510 in a highly aggressive in vivo orthotopic rat C6 glioma model where BPM 31510 was administered in combination with radiotherapy. In a pancreatic xenograft mouse model, we previously reported that BPM 31510 impacted the immune cells in the TME by increasing absolute number of infiltrated CD8+ T-cells and decreasing absolute number of infiltrated CD4+ T-cells. Moreover, an ex vivo study of PBMC’s from healthy volunteers suggests that BPM 31510 increases T-cell viability and function while also decreasing T-cell exhaustion. Currently, an ongoing first-line phase 2b study of BPM 31510 in glioblastoma in combination with radiotherapy and temozolomide will assess the clinical efficacy and potential for mechanistic synergy of multiple ROS-inducing mitochondrial mediated regimens on this aggressive cancer phenotype. BPM 31510 will be assessed in this study to provide further evidence for the impact of ROS on immunomodulation. Taken together, BPM 31510 increases mitochondrial ROS/OXPHOS in cancer cells while impacting TME-related immune cell modulation. Citation Format: Stephane Gesta, Maria D. Nastke, Seema Nagpal, Lawrence Recht, Michael A. Kiebish, Niven R. Narain, Vijay R. Modur. BPM 31510: Targeting the tumor microenvironment (TME) via mitochondrial-mediated ROS production 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 (6Suppl): Abstract nr 6518.
Gesta et al. (Fri,) studied this question.