Peer-reviewed article
BIOL-21. PATIENT-DERIVED, THREE-DIMENSIONAL ORGANOID PLATFORM FOR PEDIATRIC BRAIN TUMOR MODELING AND THERAPEUTIC TESTING
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Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a laboratory research paper about developing three-dimensional organoid models from pediatric brain tumor tissue for testing cancer treatments. The work describes a method for growing tumor tissue samples in culture and demonstrates the use of CAR-T cell therapy testing on these models. While the research may eventually inform treatment approaches for children with brain cancer, it is primarily a technical and biological study rather than research on child well-being outcomes.
Key points
Limitations
This document does not evaluate outcomes for children with brain tumors or assess the impact of any intervention on child health or well-being. It is a preclinical laboratory study focused on developing tools for future research.
Abstract
Abstract Brain tumors are the leading cause of cancer-related death in children. An important hurdle to scientific and clinical progress in the field has been the limited availability of preclinical tumor models. In recent years, the Children’s Brain Tumor Network (CBTN) has accelerated the development of patient-derived cell lines and xenografts, offering these resources to the community through open-source access. While these models are extremely valuable, their development process can be lengthy and result in clonally selected lines which presents a challenge for studying complex tumor biology. To address the need for three-dimensional tissue culture, our group in conjunction with CBTN, generates organoids from fresh tissue specimens obtained directly from surgical resection. This effort resulted in numerous organoid models generated for high-grade glioma (HGG), medulloblastoma, ependymoma, atypical teratoid-rhabdoid tumor, and low-grade glioma tumors. The tissue was processed within an hour post-extraction and cultured in growth factor-free media. Organoid formation and growth were observed as early as in 2 weeks post initiation and continued for up to three months. Banked organoids established growth upon return to culture and resembled similar cell composition to those in the original culture. This provides an excellent preclinical testing model for precision medicine-driven trials. To represent this, we utilized CAR-T testing approach and treated GD2-positive HGG organoids with GD2 CAR-T cells and control CD19 CAR-T cells. 72h exposure to GD2 CAR-T induced morphological changes and significant increase in dead cells within organoids, which was not observed in CD19 CAR-T treated counterparts (p<0.05). Here we provide a simple and efficient workflow for the generation and testing of three-dimensional tumor organoid models generated from fresh surgical tissue. The platform can accelerate not only tumor biology explorations but also empower a diverse array of precision medicine-driven testing for pediatric brain tumors.