Organoid-based platforms for oncolytic virus discovery and optimization: Bridging in vitro innovation and clinical translation.

Although oncolytic virus therapy has shown promising efficacy in preclinical studies, its clinical translation remains limited because conventional experimental models fail to replicate the human tumor microenvironment accurately. As an advanced three-dimensional culture system, organoid technology provides a powerful platform to address this challenge, as it retains the heterogeneity and microenvironmental features of primary tumors. This review systematically summarizes organoid modeling technology and highlights its critical role in the research and development of oncolytic viruses. The development of organoid biobanks, together with their integration into high-throughput screening systems, has facilitated rational viral engineering and targeted optimization through large-scale data analysis. In clinical applications, patient-derived organoids have enabled personalized prediction of therapeutic responses by serving as functional models for drug testing. Despite ongoing challenges in protocol standardization and in accurately simulating the immune microenvironment, organoid technology is rapidly becoming a key bridge between basic research and clinical translation in oncolytic virotherapy, accelerating the development of next-generation oncolytic virus therapies.