BIOL-13. DEPLOYING NEW MODELS OF NF-1 MUTANT LOW GRADE GLIOMA TO ACCELERATE THERAPEUTIC DEVELOPMENT

Pediatric low grade glioma (pLGG) research is hampered by a paucity of genetically accurate cell line models and xenografts. To address this need, we have developed and characterized multiple in vivo and organoid models. We used cell reprogramming conditions (CRC) to establish and propagate JHH-NF1-PA1, a NF1-mutant line derived from a low grade optic pathway glioma of a patient with type 1 neurofibromatosis. JHH-NF1-PA1 cells persist and take up midline positions when xenografted into the brains of zebrafish, allowing testing of therapeutics in vivo. We developed a human iPSC-brain organoid system comprising of midline neurons, glia, and microglia, largely recapitulating the microenvironment of midline low grade glioma. Our JHH-NF1-PA1 cells incorporate into these brain organoids, allowing us to test potential therapeutics in an in vitro setting in which the tumor cells grow in the appropriate microenvironment. We have also further defined the mouse BL6 NF1 null glioma cell line 1810, which forms orthotopic xenografts in mice. This last model will be useful for therapeutic testing in a syngeneic BL6 background, allowing assessment of immune infiltration and signaling downstream of NF1 loss and potential immunotherapeutics. Together, these in vitro and in vivo models of NF1-driven low grade glioma make an important contribution to our understanding of the biology of low grade glioma.