Zheng Yiyang, Pei Yusheng, Dong Chunyan, Liang Jinghui, Cai Tong, Zhang Yuan, Tan Dejiang, Wang Junzhi, He Qing
State Key Laboratory of Drug Regulatory Sciences, National Institutes for Food and Drug Control, Beijing 102629, China.
Vaccines (Basel). 2025 Aug 20;13(8):880. doi: 10.3390/vaccines13080880.
Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval of Teserpaturev/G47Δ for malignant glioma in Japan in 2021. This review synthesizes the key preclinical and clinical advancements in oHSV therapy over the last decade, critically analyzing the core challenges in target selection, genetic modification, administration routes, and targeted delivery. Key findings indicate that arming oHSV with immunomodulatory transgenes, such as cytokines and antibodies, and combining it with immune checkpoint inhibitors are critical strategies for enhancing therapeutic efficacy. Future research will focus on precision engineering using CRISPR/Cas9, the development of novel delivery vehicles like nanoparticles and mesenchymal stem cells (MSCs), and biomarker-guided personalized medicine, aiming to provide safer and more effective solutions for refractory cancers. This review synthesizes oHSV advances and analyzes novel delivery and gene-editing strategies.
溶瘤病毒（OV）免疫疗法，尤其是溶瘤单纯疱疹病毒（oHSV）免疫疗法，已成为癌症治疗中一种前景广阔的新策略。该领域已取得重大临床进展，其中的亮点包括2015年美国食品药品监督管理局（FDA）批准塔利莫基因拉帕里韦克（T-VEC）用于治疗黑色素瘤，以及2021年日本批准特塞罗帕替夫/ G47Δ用于治疗恶性胶质瘤。本综述总结了过去十年oHSV治疗在临床前和临床方面的关键进展，批判性地分析了在靶点选择、基因改造、给药途径和靶向递送方面的核心挑战。主要研究结果表明，用细胞因子和抗体等免疫调节转基因武装oHSV，并将其与免疫检查点抑制剂联合使用，是提高治疗效果的关键策略。未来的研究将集中在利用CRISPR/Cas9进行精准工程改造、开发纳米颗粒和间充质干细胞（MSC）等新型递送载体，以及生物标志物引导的个性化医疗，旨在为难治性癌症提供更安全、更有效的解决方案。本综述总结了oHSV的进展，并分析了新型递送和基因编辑策略。
