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Review
. 2014 Jun 20:5:303.
doi: 10.3389/fmicb.2014.00303. eCollection 2014.

Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy

Jianfang Ning  1 , Hiroaki Wakimoto  1
Affiliations
Review

Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy

Jianfang Ning et al. Front Microbiol. .

Abstract

Oncolytic viruses (OV) are a class of antitumor agents that selectively kill tumor cells while sparing normal cells. Oncolytic herpes simplex virus (oHSV) has been investigated in clinical trials for patients with the malignant brain tumor glioblastoma for more than a decade. These clinical studies have shown the safety of oHSV administration to the human brain, however, therapeutic efficacy of oHSV as a single treatment remains unsatisfactory. Factors that could hamper the anti-glioblastoma efficacy of oHSV include: attenuated potency of oHSV due to deletion or mutation of viral genes involved in virulence, restricting viral replication and spread within the tumor; suboptimal oHSV delivery associated with intratumoral injection; virus infection-induced inflammatory and cellular immune responses which could inhibit oHSV replication and promote its clearance; lack of effective incorporation of oHSV into standard-of-care, and poor knowledge about the ability of oHSV to target glioblastoma stem cells (GSCs). In an attempt to address these issues, recent research efforts have been directed at: (1) design of new engineered viruses to enhance potency, (2) better understanding of the role of the cellular immunity elicited by oHSV infection of tumors, (3) combinatorial strategies with different antitumor agents with a mechanistic rationale, (4) "armed" viruses expressing therapeutic transgenes, (5) use of GSC-derived models in oHSV evaluation, and (6) combinations of these. In this review, we will describe the current status of oHSV clinical trials for glioblastoma, and discuss recent research advances and future directions toward successful oHSV-based therapy of glioblastoma.

Keywords: combination therapy; gene therapy; glioblastoma; glioblastoma stem cells; herpes simplex virus type 1; molecular targeted therapy; oncolytic virus; synergy.

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Figures

Figure 1
Figure 1
Two-phasic process that oHSV-based strategies go through toward successful GBM tumor elimination. For each phase, representative interventional approaches that we discussed in the text are listed on the right.
See this image and copyright information in PMC

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References

    1. Abe T., Wakimoto H., Bookstein R., Maneval D. C., Chiocca E. A., Basilion J. P. (2002). Intra-arterial delivery of p53-containing adenoviral vector into experimental brain tumors. Cancer Gene Ther. 9, 228–235 10.1038/sj.cgt.7700437 - DOI - PubMed
    1. Advani S. J., Markert J. M., Sood R. F., Samuel S., Gillespie G. Y., Shao M. Y., et al. (2011). Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1. Gene Ther. 18, 1098–1102 10.1038/gt.2011.61 - DOI - PMC - PubMed
    1. Advani S. J., Mezhir J. J., Roizman B., Weichselbaum R. R. (2006). ReVOLT: radiation-enhanced viral oncolytic therapy. Int. J. Radiat. Oncol. Biol. Phys. 66, 637–646 10.1016/j.ijrobp.2006.06.034 - DOI - PubMed
    1. Advani S. J., Sibley G. S., Song P. Y., Hallahan D. E., Kataoka Y., Roizman B., et al. (1998). Enhancement of replication of genetically engineered herpes simplex viruses by ionizing radiation: a new paradigm for destruction of therapeutically intractable tumors. Gene Ther. 5, 160–165 10.1038/sj.gt.3300546 - DOI - PubMed
    1. Aghi M. K., Liu T. C., Rabkin S., Martuza R. L. (2009). Hypoxia enhances the replication of oncolytic herpes simplex virus. Mol. Ther. 17, 51–56 10.1038/mt.2008.232 - DOI - PMC - PubMed