In vivo three dimensional MRI of GL261 syngeneic gliomas concurrently with analysis of CNS infiltrating tumor-specific killer T cell responses (127.15)

Abstract Glioblastoma multiforme (GBM) is among the most lethal of cancers. Enhancing anti-tumor killer T cell responses via dendritic cell vaccines has correlated with a positive outcome in selected GBM patients. Nevertheless, the mechanisms by which killer T cell responses to GBM are inhibited or enhanced remain poorly defined. We therefore developed the GL261 “Quad Cassette” glioma cell line that expresses model T cell epitopes in the immunocompetent C57BL/6 mouse. Tumor size and inflammatory profiles observed in these animals was then compared to C57BL/6 mice administered the parent GL261 glioma cell line. Resulting tumors present with a tumor mass surrounded by considerable edema visible by gadolinium enhanced T1 and T2 weighted MRI. Both edema and tumor mass visible by MRI were quantified using Analyze 10.0 software which enables 3D volumetric analysis of MRI images. C57BL/6 mice with GL261 “Quad Cassette”, but not parent GL261 gliomas, presented with smaller tumor mass and significant brain infiltrating tumor specific Kb:ova specific CD8 T cells. We therefore conclude that the GL261 Quag Cassette system is suitable for studying tumor epitope specific CD8 T cell responses using the vast genetic and immunologic resources available for the C57BL/6 mouse background. Furthermore, incorporation of the first true 3D volumetric analysis of GL261 glioma size with small animal MRI will enable investigation of immunotherapeutic treatments in vivo without euthanizing the animal.