Mouse Model of Viral-Induced Brain Tumor and Generation of a Stable Tumor-Derived Cell Line

Glioblastoma (GBM) is one of the most common and aggressive primary brain tumors. The median survival following diagnosis is about 14 to 16 months, even with the standard of care treatment. In recent years, there has been considerable progress in the field of immunotherapy, particularly with the use of peptide and cell-based cancer vaccines, for treating GBM. However, current clinical trials for vaccination in GBM have not demonstrated satisfactory results. Successful clinical translation of cancer vaccines relies on rigorous evaluation in pre-clinical animal models, so the choice of an appropriate animal model is crucial for the assessment of cancer vaccines. Here, we describe a model of brain tumor in immunocompetent mice using Cre recombinase (Cre)-inducible lentiviral vectors which can be used to initiate tumors from different cells in the central nervous system. This protocol describes the isolation and concentration of high titer lentivirus by transfection of HEK 293 T cells and the induction of gliomas using this virus, through stereotactic injection to the mice brain. Moreover, this protocol also provides a step-by-step description of the tumor dissociation and the creation and validation of a tumor-derived cell line, which can be used for in vitro assays as well as for developing new primary murine tumors and re-challenging the mice.