Abstract 3931: Establishment of an orthotopic intracranial luciferase labelled patient derived xenograft of glioblastoma in immunocompromised mice model
Authors: Seth Hannah, Fu-Ju Chou, Ksenia Vulikh, Mara Gilardi, Stefano Cairo, Paul Heverly
Journal: Cancer Research (2025)

Abstract Glioblastoma multiforme (GBM) is the most aggressive and fatal form of brain cancer, with a median survival time of less than 15 months. Currently, GBM patients have limited treatment options and poor efficacy outcomes, underscoring the urgent need for innovative research methods and more effective therapeutic strategies. Patient-derived xenografts (PDX) offer a promising approach to evaluate the side effects and potency of drugs in vivo. By implanting GBM patient tumor samples into immunocompromised mice, we gain invaluable insights into the unique mutations and genetic profiles of individual GBM models. PDX models provide a more accurate and personalized approach compared to traditional cell line-based studies. Intracranial xenograft techniques emulate the interaction of brain tumors with complex brain microenvironment and the blood-brain barrier, offering significant advantages for testing new regimens for brain tumors. Non-invasive imaging techniques like MRI and in vivo imaging systems (IVIS) have traditionally been used to monitor intracranial tumor growth and treatment response. However, challenges such as achieving the expected resolution with mouse MRI, long scan times, high costs, and technical barriers in labeling PDX material limit their application. This study aims to establish a pre-clinically relevant platform for the development and validation of potential pharmaceutical treatments for glioblastoma, utilizing patient-derived cells within an appropriate tumor microenvironment. To create this model, U87 and patient-derived glioblastoma cells were labeled with luciferase and cultured ex vivo to confirm bioluminescent signal integrity. Using a stereotaxic apparatus and established skull-to-brain mapping techniques, cell suspensions were implanted into predetermined cortical coordinates. The bioluminescent signal from the proliferating tumor was monitored, revealing consistent exponential growth of the orthotopically implanted tumor without adverse health effects over a 28-day period. Our findings demonstrate that this method allows for the orthotopic implantation of human patient-derived glioblastoma in immunocompromised mice, fostering tumor development within a relevant microenvironment. This model provides a robust platform for the accurate testing and development of glioblastoma therapeutics. Preliminary IVIS data indicate that the intensity of the U87-Luc tumor increased significantly over a designated time period. Similarly, the PDX-GBM Luc showed a remarkable increase as well. This new orthotopic intracranial platform enables us to monitor tumor growth through bioluminescent measurements, offering a valuable tool for advancing glioblastoma research and treatment. Citation Format: Seth Hannah, Fu-Ju Chou, Ksenia Vulikh, Mara Gilardi, Stefano Cairo, Paul Heverly. Establishment of an orthotopic intracranial luciferase labelled patient derived xenograft of glioblastoma in immunocompromised mice model [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 3931.