{
  "abstract": "Background Immunologically cold tumors characterized by immune exclusion and metabolic suppression typically exhibit poor responses to immune checkpoint inhibitors (ICIs). BPM31510, a novel lipid nanoparticle that delivers high levels of oxidized coenzyme Q10 (CoQ10), represents a potential therapeutic approach for further investigation by generating mitochondrial ROS leading to tumor cell apoptosis and remodeling the tumor microenvironment (TME). This study investigates how BPM31510 transforms the immuno-metabolic landscape within a syngeneic murine tumor model, potentially sensitizing tumors to ICI therapy.Methods Female C57BL/6N mice bearing MC38-CEA tumors were treated intraperitoneally with BPM31510 (100 or 300 mg/kg) or vehicle every other day. Comprehensive immune profiling was performed via flow cytometry on tumors harvested at strategic intervals (Days 8–16) evaluating lymphoid and myeloid populations, checkpoint receptor expression (CTLA-4, PD-1, Lag-3), and PD-L1 distribution across immune and tumor compartments. Spatial omics technology was employed to precisely map immune infiltration patterns and metabolic signatures within the TME. Serum and lymph nodes were preserved for subsequent correlative analyses.Results BPM31510 demonstrated dose-dependent tumor growth inhibition, achieving 15% and 33% efficacy at 100 mg/kg and 300 mg/kg doses, respectively, by Day 16. Early response dynamics (Days 10–14) at 100 mg/kg revealed enhanced infiltration of CD8+ T cells, dendritic cells, and diverse myeloid populations, concurrent with reduced immunosuppressive tumor-associated macrophages (TAMs), particularly M2 phenotypes. By Day 16, the 300 mg/kg dose further amplified these immunomodulatory effects and significantly downregulated CTLA-4, PD-1, and Lag-3 expression on both CD4+ and CD8+ T cells. Spatial omics analysis identified newly formed immune-rich niches within BPM31510-treated tumors that correlated with distinct metabolic reprogramming signatures. While PD-L1 expression moderately increased on dendritic cells and granulocytes, tumor cell PD-L1 remained unchanged. Collectively, these findings demonstrate BPM31510’s capacity to convert an immune-cold TME into an immune-active state.Conclusions BPM31510 exhibits a multifaceted mechanism that simultaneously reinvigorates anti-tumor immunity and recalibrates tumor metabolism, fundamentally transforming the immune architecture of previously cold tumors. Through enhanced T cell recruitment and reduced inhibitory checkpoint expression, BPM31510 creates conditions favorable for ICI response, positioning it for further investigation as a potential candidate for combination immunotherapy regimens. Ongoing investigations focus on identifying the cellular origins of observed metabolic alterations and further characterizing BPM31510’s potential to synergize with established checkpoint therapies to overcome treatment resistance.",
  "authors": [
    {
      "affiliations": [
        "BPGbio, Waltham, MA, USA"
      ],
      "name": "Maria-Dorothea Nastke"
    },
    {
      "affiliations": [
        "BPGbio, Waltham, MA, USA"
      ],
      "name": "Sylwia Stopka"
    },
    {
      "affiliations": [
        "BPGbio, Waltham, MA, USA"
      ],
      "name": "Juan J Aristizabal-henao"
    },
    {
      "affiliations": [
        "BPGbio, Waltham, MA, USA"
      ],
      "name": "Kaila M Bennett"
    },
    {
      "affiliations": [
        "BPGbio, Waltham, MA, USA"
      ],
      "name": "Archna Ravi"
    },
    {
      "affiliations": [
        "BPGbio, Waltham, MA, USA"
      ],
      "name": "Srada Karmacharya"
    },
    {
      "affiliations": [
        "BPGbio, Waltham, MA, USA",
        "University of Miami Miller School of Medicine, Miami, FL, USA"
      ],
      "name": "Niven R Narain"
    },
    {
      "affiliations": [
        "BPGbio, Waltham, MA, USA"
      ],
      "name": "Michael A Kiebish"
    },
    {
      "affiliations": [
        "BPGbio, Waltham, MA, USA"
      ],
      "name": "Stephane Gesta"
    }
  ],
  "title": "1191 BPM31510, a CoQ10-lipid nanoparticle, remodels the tumor microenvironment through immuno-metabolic reprogramming in syngeneic models",
  "uid": "15a3f3c6-6dce-511c-a614-91d1b006cbfb"
}