Oncolytic immunovirotherapy as an agnostic vaccination against glioblastoma

High grade gliomas (HGG) are aggressive tumors characterized by high heterogeneity, immune modulated environment and resiliency to standard treatments. Despite the HGG frequency is about 5 people every 100000, the overall survival (OS) rate at one year is extremely low. Standard of care treatments are invasive and never resolving while alternative approaches like immunotherapy and oncolytic virotherapy are showing promising outcomes. In this thesis are discussed the results obtained by the employment of an innovative therapy based on the combination of immunotherapy and oncolytic virotherapy. A new oncolytic HSV, R-115, has been evaluated for its ability to increase survival and rescue immunocompetent mice previously injected with murine HGG. The effects of R-115 immunovirotherapy were tested in two murine models, based on completely or partially targetable cells, respectively. The analyses were also focused on the ability of R-115 treatment to induce an immune memory which prevented secondary transplanted tumors and prolonged survival when administered as cell therapy. Altogether, our investigations candidate R-115 as a valuable alternative to common treatments and encourage further investigation to evaluate its potential for clinical application.