MODL-42. ESTABLISHMENT AND CHARACTERIZATION OF A NOVEL MOUSE SYNGENEIC GLIOBLASTOMA CELL LINE

Abstract

Abstract Glioblastoma (GBM) is the most common and the deadliest type of brain tumor affecting the adult central nervous system, carrying a median survival of 14 months. In vivo syngeneic animal models of GBM that recapitulate human GBM are urgently needed to decipher glioma biology and develop novel therapeutics, including immunotherapy. Here, we generated a syngeneic mouse glioblastoma stem cell line (RCAS-TVA-GSC01) through repeated in-vitro passages of stem-like tumor cells isolated from the RCAS-TVA glioma mouse model, which overexpresses PDGFA and carries a homozygous deletion of Ink4a-Arf locus. We characterized this new GSC line both in vitro and in vivo. This cell line expresses stemness markers CD133 and Nestin, and is able to differentiate into astrocyte, neuron, and oligodendrocyte-like cells in 2% FBS differentiating medium with markers GFAP, β-III tubulin, and O4, respectively. Transcriptomic and genomic profiling of RCAS-TVA-GSC01 cells revealed molecular heterogeneity comparable to human glioblastoma. When intracranially transplanted into wild-type C57BL/6 mice, this cell line formed high-grade gliomas with a median survival time of 56.5 days. The differentiation potential and molecular heterogeneity make RCAS-TVA GSC01 line a unique and useful tool for studying multiple aspects of glioblastoma pathogenesis and a promising platform for testing new GBM therapeutics study, especially for immunotherapy that requires a syngeneic mouse model.