TMOD-09. A PATIENT-DERIVED XENOGRAFT MODEL MIMICKING RECURRENT PEDIATRIC MALIGNANT GLIOMA

Abstract

Abstract BACKGROUND: Pediatric high grade glioma (pHGG) is a devastating cancer of the central nervous system. The prognosis of this most malignant form of brain tumor remains poor, largely due to the inherent resistance of pHGG to therapy, and inevitably leads to recurrence. Unfortunately, because recurrent glioma, or glioma remaining after conventional therapy, frequently has very different molecular characteristics from the original tumor in addition to a vastly different biological behavior, recurrent pHGG has proven exceedingly difficult to treat, with very few treatment options providing clinically meaningful outcomes. As part of the NCI Pediatric Preclinical Testing Program, several pediatric brain cancer cell lines, including the ones used in this study, were developed and characterized. However, to our knowledge, none have been utilized in development of a rat xenograft model of recurrent pHGG. METHODS: Pediatric glioblastoma cells (SJ-GBM2) were obtained from the Children’s Oncology Group Cell Culture and Xenograft Repository. Irradiated SJGBM2-10gy cells were generated by exposure to a total radiation dose of 10 Gy. Following irradiation, the resultant SJGBM2-10gy cells were tested for cell viability and allowed to reach confluence prior to stereotactical implantation into the right striatum of male athymic rats. RESULTS: Less than 1% of total cells survived radiation. Both irradiated and parental cell lines formed tumors in 100% of the animals following intracranial implantation. Irradiated SJGBM2-10gy cells exhibited a more aggressive tumor growth than the parental SJ-GBM2 cell line, resulting in mortality on average 14 days earlier. Histopathological analysis is underway and more advanced imaging studies are planned. CONCLUSION: To our knowledge this is the first report of an intracranial rat xenograft model mimicking recurrent pHGG using irradiated cell lines. It represents a robust and expedient in vivo model for studying recurrent pHGG biology.