溶瘤病毒的免疫学机制及临床研究进展

溶瘤病毒（oncolytic virus，OVs）历经百年发展，应用于当前最具潜力的肿瘤免疫疗法。它主要是天然的或基因修饰的DNA病毒和RNA病毒。近年来随着基因工程技术的飞跃发展，经基因改造的溶瘤病毒在肿瘤治疗领域取得很大进展，很多不同类型的病毒（包括单纯疱疹病毒、腺病毒、痘病毒、麻疹病毒和呼肠孤病毒等）正处于临床前研究、临床试验阶段或已批准上市，显示了良好的安全性和临床疗效。普遍认为溶瘤病毒靶向杀伤肿瘤细胞是通过选择性在肿瘤细胞内自我复制，最终裂解肿瘤细胞，同时可激发机体的免疫应答反应，进而增强抗肿瘤免疫效果，靶向杀伤肿瘤细胞而对正常细胞无明显影响。运用基因重组技术将溶瘤病毒与免疫检查点相结合以及肿瘤免疫联合疗法的兴起和不断进步，使溶瘤病毒的应用更加广泛，但仍存在病毒靶向性、安全性、给药途径等瓶颈问题。本文综述了溶瘤病毒的发展史、病毒分类、不同类型溶瘤病毒产品的临床研究进展、溶瘤病毒靶向杀伤肿瘤的免疫学机制及未来发展面临的挑战与展望等。

Immunologic Mechanisms and Clinical Research Progress of Oncolytic Viruses

Oncolytic viruses (OVs) have been investigated for a century and have become one of the most advanced types of tumor immunotherapy. It is primarily a natural or genetically modified viruses, including DNA and RNA viruses. In recent years, with the rapid development of genetic engineering technology, the gene-modified oncolytic viruses have made great progress in the field of tumor treatment, several types of viruses (including HSV, adenovirus, poxvirus, measles virus, reovirus etc.) are currently in preclinical studies, clinical trials or have been approved in clinic, showing good safety and clinical efficacy. It is generally believed that oncolytic viruses target and kill tumor cells by selectively replicating themselves in tumor cells, and finally lysing and killing tumor cells. At the same time, they can stimulate the immune responses of the body, thus enhancing the antitumor immunity, the tumor cells can be targeted and killed with no obvious side effects. The combination of oncolytic virus and immune checkpoint by gene recombination and the breakthrough of tumor immunotherapy have made the application of oncolytic virus more extensive, however, there are still some bottleneck problems such as virus targeting, security and administration route. This review provides a comprehensive and detailed overview of the development of oncolytic viruses. We list some viruses have been used as candidates for lysis of cancer cells and the clinical trials in the field of oncolytic virotherapy. And we discuss about the immunological mechanism of oncolytic virus targeting to kill tumors, and the challenges and prospects in the future.