Anti-viral Immunity in the Tumor Microenvironment: Implications for the Rational Design of Herpes Simplex Virus Type 1 Oncolytic Virotherapy
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Purpose of Review
The design of novel herpes simplex type I (HSV-1)–derived oncolytic virotherapies is a balancing act between safety, immunogenicity, and replicative potential. We have undertaken this review to better understand how these considerations can be incorporated into rational approaches to the design of novel herpesvirus oncolytic virotherapies.
Several recent papers have demonstrated that enhancing the potential of HSV-1 oncolytic viruses to combat anti-viral mechanisms present in the tumor microenvironment leads to greater efficacy than their parental viruses.
It is not entirely clear how the immunosuppressive tumor microenvironment affects oncolytic viral replication and spread within tumors. Recent work has shown that the manipulation of specific cellular and molecular mechanisms of immunosuppression operating within the tumor microenvironment can enhance the efficacy of oncolytic virotherapy. We anticipate that future work will integrate greater knowledge of immunosuppression in tumor microenvironments with design of oncolytic virotherapies.
KeywordsHSV Oncolytic Herpesvirus VC2
We thank Dr. Rhonda Cardin and Dr. Rafiq Nabi for the helpful discussions in the preparation of this manuscript. This work was supported by the Louisiana Board of Regents Governor’s Biotechnology grant to K.G.K and Core Facilities supported by NIH:GM103424 and NIH GM110760. PJFR is funded by a National Institutes of Health COBRE grant (P20 GM121288).
Compliance with Ethical Standards
Conflict of Interest
Dr. Kousoulas reports non-financial support from Ios Biomedical Group, Inc. (IBG), outside the submitted work; in addition, Dr. Kousoulas has a patent “vaccines against genital herpes infections” (Patent number: 10130703) licensed to Ios Biomedical Group, Inc., and a patent “synthetic herpes simplex viruses type-1 for treatment of cancers” (Patent number: 8586028) issued.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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