Virus-Based Immunotherapy of Glioblastoma

Abstract

Glioblastoma (GBM) is the most common type of primary brain tumor in adults. Despite recent advances in cancer therapy, including the breakthrough of immunotherapy, the prognosis of GBM patients remains dismal. One of the new promising ways to therapeutically tackle the immunosuppressive GBM microenvironment is the use of engineered viruses that kill tumor cells via direct oncolysis and via stimulation of antitumor immune responses. In this review, we focus on recently published results of phase I/II clinical trials with different oncolytic viruses and the new interesting findings in preclinical models. From syngeneic preclinical GBM models, it seems evident that oncolytic virus-mediated destruction of GBM tissue coupled with strong adjuvant effect, provided by the robust stimulation of innate antiviral immune responses and adaptive anti-tumor T cell responses, can be harnessed as potent immunotherapy against GBM. Although clinical testing of oncolytic viruses against GBM is at an early stage, the promising results from these trials give hope for the effective treatment of GBM in the near future.

Keywords: cancer immunotherapy; glioblastoma; oncolytic virotherapy.

Figure 1

Schematic picture summarizing the events and factors related to successful oncolytic immunotherapy (A), and to limited effectiveness of oncolytic viruses (B) in GBM. Abbreviations: BBB: blood–brain barrier, GBM: glioblastoma, TAA: tumor-associated antigen, NAb: neutralizing antibody, APC: antigen-presenting cell, CNS: central nervous system, GSC: glioma stem cell, NK: natural killer cell.