背景：溶瘤病毒疗法（OVT）是一种有前途的抗肿瘤方式，它利用溶瘤病毒（OVs）优先攻击癌症而不是正常组织。随着对病毒和肿瘤细胞特性的了解，许多创新的OV被设计用来征服癌症，例如塔利莫根拉赫帕雷普维奇(T-VEC)和塔萨纳托雷夫(DNX-2401)。然而,必须进一步优化和平衡治疗安全性和有效性，以确保临床上的OVT具有出色的安全性和有效性，合理的联合治疗策略也是值得探讨的重要挑战。
方法：在这里，我们对OVT的发展历史和现状进行了严格的回顾，强调提高安全性和有效性的机制。我们认为溶瘤病毒疗法已经发展成为第四代肿瘤免疫疗法。特别是,通过设计表达双特异性T细胞激活剂（BiTA）的OV来激发T细胞是一种用一块石头杀死两只鸟的有希望的策略。OVs和免疫细胞的治疗策略的惊人组合赋予了管理癌症的巨大潜力。此外，最近讨论了有吸引力的临床前OVT，并对临床试验中的OVT进行了系统评价。
结论：OVs，正在进入临床试验，即将成为临床抗肿瘤药物的前沿。
Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With the understanding particularly in the characteristics of viruses and tumor cells, numerous innovative OVs have been engineered to conquer cancers, such as Talimogene Laherparepvec (T-VEC) and tasadenoturev (DNX-2401). However, the therapeutic safety and efficacy must be further optimized and balanced to ensure the superior safe and efficient OVT in clinics, and reasonable combination therapy strategies are also important challenges worthy to be explored.
Here we provided a critical review of the development history and status of OVT, emphasizing the mechanisms of enhancing both safety and efficacy. We propose that oncolytic virotherapy has evolved into the fourth generation as tumor immunotherapy. Particularly, to arouse T cells by designing OVs expressing bi-specific T cell activator (BiTA) is a promising strategy of killing two birds with one stone. Amazing combination of therapeutic strategies of OVs and immune cells confers immense potential for managing cancers. Moreover, the attractive preclinical OVT addressed recently, and the OVT in clinical trials were systematically reviewed.
OVs, which are advancing into clinical trials, are being envisioned as the frontier clinical anti-tumor agents coming soon.
