Progress in the research and development of oncolytic virus therapies

Yiran LiQin XiChenggang Liang^*Lan Wang^*

• National Institutes for Food and Drug Control (China), Beijing, China

Oncolytic viruses (OVs) are a class of viral preparations with selective replication capability in tumor cells and the ability to activate systemic anti-tumor immunity. They have emerged as an important breakthrough in cancer treatment following chemotherapy, targeted therapy, and immune checkpoint inhibitors. This article systematically reviews the developmental trajectory of OVs from the accidental discovery of wild strains to their genetic engineering-based modification and optimization, and subsequently to accelerated clinical translation. It primarily highlights key advances in viral backbone design, immune regulatory gene insertion, and combination therapy strategies. Currently, several OV-based therapeutics have been approved for clinical use worldwide for the treatment of various solid tumors, including melanoma, glioblastoma, and head and neck cancers, demonstrating their extensive potential for broader indication coverage as evidenced by ongoing clinical trials. Although OVs possess unique advantages in their ability to remodel the tumor microenvironment and elicit both local and systemic anti-tumor effects, their clinical application still faces challenges such as limited monotherapy efficacy, barriers to systemic delivery, a lack of precision biomarkers, and issues in large-scale manufacturing and quality control. Looking ahead, by drawing on cutting-edge technologies such as CRISPR-based gene editing, reverse genetics, advanced delivery systems, and multimodal combination therapy, OVs are expected to achieve greater precision and personalization in cancer treatment, thereby promoting their wider application in the management of solid tumors.