Abstract 2774: Longitudinal characterization of patient-derived orthotopic xenograft brain tumor models

Abstract

Gliomas are the most common primary brain tumors and currently the prognosis is still poor. Due to this, it is one of the main areas in oncological research and drug development programs. Innovative therapies are vital to improve treatment outcomes but must be developed to enable trafficking across the blood brain barrier (BBB). For this advent, animal models provide important information prior to clinical studies. Among the different in vivo models, orthotopic PDX models represent best the tumor microenvironment and natural variability of tumors, hence providing the most reliable results over species. In the brain tumor field, imaging has a central role in clinical diagnosis and as a prognostic factor to monitor therapy response in patients. Magnetic resonance imaging (MRI) is widely used for clinical diagnosis and disease follow up as it offers unprecedented soft tissue contrast and high spatial resolution non-invasive way. In addition to imaging, molecular profiling, e.g. circulating immune biomarkers and local oncometabolites in the tumor environment may facilitate as important translational biomarkers in development of immunotherapy for gliomas in addition to traditional histopathological readouts. The purpose of this work was to analyze possible heterogeneity of tumors in vivo, growth rate and volume in stereotactically implanted orthotopic PDX brain tumor models using MRI/MRS imaging. In addition to imaging, neurological scoring was performed to monitor general animal welfare, cytokine profiles from plasma to observe immunological responses over time and determination of oncometabolites in plasma and brain tissues combined with traditional histopathological changes were performed. The data from orthotopic models was also compared to readouts in subcutaneous models. As a conclusion, translational in vivo imaging techniques were applied to study orthotopic tumor progression combined with circulating immune biomarkers, and general welfare scoring. These readouts provide a powerful and translational research tool together with oncological disease animal models allowing comprehensive evaluation of disease progression and treatment interventions for in vivo studies. Citation Format: Julia Schueler, Mariette Heins, Artem Shatillo, Kimmo Lehtimäki, Anne-Lise Peille, Taina-Kaisa Stenius, Timo Bragge, Jussi Rytkönen, Diana Miszczuk, Tuulia Huhtala. Longitudinal characterization of patient-derived orthotopic xenograft brain tumor models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2774.