Rider Paul J F, Uche Ifeanyi K, Sweeny Larissa, Kousoulas Konstantin G
Division of Biotechnology and Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Louisiana State University Health Sciences Center, New Orleans, Louisiana USA.
Curr Clin Microbiol Rep. 2019 Dec;6(4):193-199. doi: 10.1007/s40588-019-00134-3. Epub 2019 Nov 26.
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.
新型单纯疱疹病毒I型（HSV-1）衍生的溶瘤病毒疗法的设计是在安全性、免疫原性和复制潜力之间进行权衡。我们进行本综述是为了更好地理解如何将这些考虑因素纳入新型疱疹病毒溶瘤病毒疗法的合理设计方法中。
最近的几篇论文表明，增强HSV-1溶瘤病毒对抗肿瘤微环境中存在的抗病毒机制的潜力，会比其亲本病毒产生更高的疗效。
目前尚不完全清楚免疫抑制性肿瘤微环境如何影响溶瘤病毒在肿瘤内的复制和传播。最近的研究表明，操纵肿瘤微环境中运行的特定免疫抑制细胞和分子机制可以提高溶瘤病毒疗法的疗效。我们预计未来的工作将把对肿瘤微环境中免疫抑制的更多了解与溶瘤病毒疗法的设计相结合。
