Abstract A017: Immunocompetent Metastatic Murine Neuroblastoma Models via Caudal Artery Injection
Matthew R. Schuelke, Ori Orbach, Tina Acholla, Timothy Spear, John M. MarisAbstract
Background:
High-risk neuroblastoma (HRNB) continues to cause significant morbidity and mortality via metastatic bone marrow disease at presentation and relapse. However, few immunocompetent murine models of metastatic HRNB exist.
Methods:
Using published techniques (Kuchimaru 2018), we injected HRNB cells from TH-MYCN genetically engineered murine models into the caudal artery of C57BL/6 mice, delivering cells to the femoral arteries with the intent of localizing tumors to the hindlimb femoral bone marrow. We used fluorescence and bioluminescence tagging to non-invasively monitor tumors via IVIS, serially sampled peripheral blood to characterize systemic immune responses, and acquired bone marrow and metastatic masses upon sacrifice for flow cytometry and immunohistochemistry.
Results:
Of the five injected subclones, three demonstrated increased take rates of 75% with hindlimb femoral bone marrow and 80% with non-bone marrow metastatic tumors. Mice succumbed to their disease between 50 and 100 days. Bone marrow and metastatic tumors had comparable surface phenotypes to flank tumors. Cell counts of PBMCs at disease progression demonstrated thrombocytopenia and anemia, but also neutrophilia, which by flow cytometry was consistent with myeloid derived suppressor cells.
Conclusion:
We developed a new immunocompetent murine model of metastatic HRNB and techniques to monitor disease progression, creating opportunities for preclinical testing and study of the tumor-immune metastatic microenvironment.
Citation Format:
Matthew R. Schuelke, Ori Orbach, Tina Acholla, Timothy Spear, John M. Maris. Immunocompetent Metastatic Murine Neuroblastoma Models via Caudal Artery Injection [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Bridging Discovery and Clinical Impact in Pediatric Cancer; 2026 Sep 22-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_1):Abstract nr A017.