Abstract 3277: Investigating the link between metabolic reprogramming and immune modulation in tumors: exploring the therapeutic potential of BPM31510

Abstract BPM31510, a CoQ10-lipid nanoparticle, has been shown in previous studies to deliver supraphysiological levels of oxidized CoQ10 to tumors, leading to the induction of mitochondrial Reactive Oxygen Species (ROS) and subsequent apoptotic cell death. Since mitochondrial metabolism is crucial for immune cell function, we investigated whether BPM31510 could influence the tumor microenvironment (TME) to influence immune-mediated tumor elimination. In tumor models such as MC38 and PAN02, we have demonstrated that BPM31510 induces cytotoxic T cell infiltration while concurrently reducing tumor-associated macrophages (TAMs). Additionally, in a rat glioblastoma (GBM) model, BPM31510 was found to metabolically reprogram tumors, further suggesting a potential link between immune modulation and metabolic changes within the TME. These findings support the hypothesis that BPM31510’s ability to reprogram tumor metabolism and induce T cell infiltration may be interconnected. This dual mechanism positions BPM31510 as a promising therapeutic for enhancing immune responses in 'immunologically cold' tumors, such as GBM and pancreatic cancer. To explore this connection further, we propose focused studies in syngeneic murine models to examine how BPM31510’s immune-modulatory and metabolic effects interact within the TME. These studies will involve detailed analysis of both tumor and lymphoid tissues using advanced flow cytometry and TIMSTOF FLEX spatial omics technology. The goal is to investigate how different dosing and scheduling regimens of BPM31510 impact the relationship between tumor metabolism, immune cell phenotype, and immune activity. Ultimately, this study aims to provide new insights into optimizing BPM31510 treatment strategies, potentially enhancing the effectiveness of immune-based therapies for these difficult-to-treat cancers. By understanding how BPM31510 influences both the immune landscape and metabolic reprogramming of tumors, we hope to develop more effective therapeutic approaches for 'cold' tumors like GBM and pancreatic cancer. Citation Format: Maria-D. Nastke, Sylwia Stopka, Abbas Khojestah, Juan J. Aristizabal-Henao, Archna Ravi, Kaila M. Bennett, Niven R. Narain, Lawrence Recht, Michael A. Kiebish, Stephane Gesta. Investigating the link between metabolic reprogramming and immune modulation in tumors: exploring the therapeutic potential of BPM31510 [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 3277.