Multiple strategies to improve the therapeutic efficacy of oncolytic herpes simplex virus in the treatment of glioblastoma

Abstract

Oncolytic viruses have attracted widespread attention as biological anticancer agents that can selectively kill tumor cells without affecting normal cells. Although progress has been made in therapeutic strategies, the prognosis of patients with glioblastoma (GBM) remains poor and no ideal treatment approach has been developed. Recently, oncolytic herpes simplex virus (oHSV) has been considered a promising novel treatment approach for GBM. However, the therapeutic efficacy of oHSV in GBM, with its intricate pathophysiology, remains unsatisfactory due to several obstacles, such as limited replication and attenuated potency of oHSV owing to deletions or mutations in virulence genes, and ineffective delivery of the therapeutic virus. Multiple strategies have attempted to identify the optimal strategy for the successful clinical application of oHSV. Several preclinical trials have demonstrated that engineering novel oHSVs, developing combination therapies and improving methods for delivering oHSV to tumor cells seem to hold promise for improving the efficacy of this virotherapy.

Keywords: antiviral immunity; armed virus; combination therapy; glioblastoma; oncolytic herpes simplex virus.

Figure 1.

Schematic description of destruction mechanism of oHSVs destroying tumor cells and multiple strategies to improve its efficacy. oHSVs directly destroy tumor cells by selectively replicating in them and evade antiviral immunity, as well as stimulate antitumor immune responses, which are main mechanisms for oHSVs to kill cancer cells. Multiple strategies can improve the efficacy of oHSVs in the treatment of tumors, including engineering novel oHSVs, increasing systemic delivery of oHSVs to tumor cells and combination therapy. oHSV, oncolytic herpes simplex virus.