A murine model for virotherapy of malignant brain tumors

Glioblastomas (GBMs) are very aggressive and almost incurable brain tumors. The development of new therapeutical approaches capable of selectively killing cancer cells could represent a step forward to fight cancer. With this aim we tested the efficacy of a novel oncolytic therapy based on recombinant herpes simplex viruses (HSVs) infecting exclusively cells expressing the human receptor HER-2 [1, 2], overexpressed in about 15% of GBMs [3]. For this study we exploited a murine GBM model based on PDGF-B embryonic transduction [4, 5]. We engineered cell cultures derived from this model to express HER-2 and we injected intracranically such cultures in NOD/SCID mice. We evaluated the efficacy of R-LM113, a recombinant HSV directed to HER-2, in this glioma model expressing HER-2. We demonstrated that mice injected with engineered glioma cells infected with R-LM113 developed gliomas with a statistically significant delay compared to mice injected with non-infected engineered glioma cells.