Fang Chao, Xiao Gaozhe, Wang Taixia, Song Li, Peng Bo, Xu Bin, Zhang Kun
Central Laboratory and Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Tongji University, No. 301 Yan-chang-zhong Road, Shanghai 200072, China.
National Center for International Research of Bio-targeting Theranostics, Guangxi Medical University, No. 22 Shuangyong Road 22, Nanning, Guangxi 530021, China.
Research (Wash D C). 2023;6:0108. doi: 10.34133/research.0108. Epub 2023 Apr 3.
Oncolytic viruses (OVs) as one promising antitumor methods have made important contributions to tumor immunotherapy, which arouse increasing attention. They provide the dual mechanisms including direct killing effect toward tumor cells and immune activation for elevating antitumor responses, which have been proved in many preclinical studies. Especially, natural or genetically modified viruses as clinical immune preparations have emerged as a new promising approach objective to oncology treatment. The approval of talimogene laherparepvec (T-VEC) by the U.S. Food and Drug Administration (FDA) for the therapy of advanced melanoma could be considered as a milestone achievement in the clinical translation of OV. In this review, we first discussed the antitumor mechanisms of OVs with an emphasis on targeting, replication, and propagation. We further outlined the state of the art of current OVs in tumor and underlined the activated biological effects especially including immunity. More significantly, the enhanced immune responses based on OVs were systematically discussed from different perspectives such as combination with immunotherapy, genetic engineering of OVs, integration with nanobiotechnology or nanoparticles, and antiviral response counteraction, where their principles were shed light on. The development of OVs in the clinics was also highlighted to analyze the actuality and concerns of different OV applications in clinical trials. At last, the future perspectives and challenges of OVs as an already widely accepted treatment means were discussed. This review will provide a systematic review and deep insight into OV development and also offer new opportunities and guidance pathways to drive the further clinical translation.
溶瘤病毒（OVs）作为一种很有前景的抗肿瘤方法，为肿瘤免疫治疗做出了重要贡献，因而受到越来越多的关注。它们具有双重作用机制，包括对肿瘤细胞的直接杀伤作用以及激活免疫以增强抗肿瘤反应，这在许多临床前研究中都得到了证实。特别是，天然或基因改造病毒作为临床免疫制剂已成为肿瘤治疗的一种新的有前景的方法。美国食品药品监督管理局（FDA）批准塔利莫基因拉赫帕里韦克（T-VEC）用于晚期黑色素瘤的治疗，可被视为溶瘤病毒临床转化的一个里程碑式成就。在本综述中，我们首先讨论了溶瘤病毒的抗肿瘤机制，重点是靶向、复制和传播。我们进一步概述了当前溶瘤病毒在肿瘤治疗中的技术现状，并强调了其激活的生物学效应，尤其是免疫效应。更重要的是，从与免疫治疗联合、溶瘤病毒的基因工程、与纳米生物技术或纳米颗粒整合以及抗病毒反应对抗等不同角度系统地讨论了基于溶瘤病毒的增强免疫反应，并阐明了其原理。还强调了溶瘤病毒在临床中的发展，以分析不同溶瘤病毒在临床试验中的应用现状和关注点。最后，讨论了溶瘤病毒作为一种已被广泛接受的治疗手段的未来前景和挑战。本综述将对溶瘤病毒的发展进行系统综述并提供深入见解，也将为推动其进一步临床转化提供新的机遇和指导途径。
