Orthotopic glioblastoma mouse model in a new shuttle session - Cost-effective & time-saving efficacy studies

04 / 23 / 2019

Our syngeneic glioma mouse model, based on the intracranial inoculation of Luc2-expressing GL261 cells and bioluminescence imaging for tumor growth monitoring, represents a suitable tool for chemo- and immunotherapy assessment. It closely mimics the human disease in terms of tumor progression and anti-tumor response, and recapitulates glioblastoma characteristic features including among others tumor immune cell infiltration and tumor-induced immunosuppression.

Model responsiveness to standard Temozolomide and immune checkpoint inhibitors i.e. anti-CTLA4, anti-PD1, and anti-PDL1 antibodies, makes it well-suited for testing candidate compounds for their efficacy, as single agents and/or in combination, in promoting anti-tumor activity.

Take this shuttle session as an opportunity to run your study

Figure 1: Orthotopic syngeneic GL261 glioblastoma model is responsive to TMZ and PD1/PDL1 axis blockade.  Mice were OT inoculated with GL261-Luc2 glioma cells and then treated with either Vehicles, temozolomide (TMZ), anti-PD1 or anti-PDL1 antibodies. Bioluminescence imaging was performed once a week starting from day7 post-tumor inoculation, on days 7, 14, 21, and 28 post-tumor cell inoculation.

Figure 2: Intracranial glioma tumor-bearing model is characterized by an immunoprivileged microenvironment.  Flow cytometry analysis of GL261 tumors shows infiltration by both lymphocytic (CD4, CD8, and Treg (FoxP3+/CD4+) subsets) and myeloid cells including the immunosuppressive MDSC population (CD11b/Gr1low-int). Those key immune cell subsets were shown to be differentially modulated upon treatment with either anti-PD1 or anti-PDL1 antibodies – Treg cell population being mainly decreased upon PD1 blockade, while anti-PDL1 antibody was shown to both increase CD8 and decrease MDSC cell infiltration.