Engineered oncolytic virus OH2-FLT3L enhances antitumor immunity via dendritic cell activation.

The combination of oncolytic viruses (OVs) with other immunotherapies, such as immunostimulatory therapies, is a current research hotspot; however, optimizing their therapeutic potential remains to be fully explored. Here, we designed a novel oncolytic herpes simplex virus 2 expressing Fms-like tyrosine kinase 3 ligand (OH2-FLT3L), which induces an antitumor cytotoxic T cell immune response by activating dendritic cells (DCs). We found that OH2-FLT3L specifically infects tumor cells, induces immunogenic cell death (ICD), and releases a large number of tumor-specific antigens, which bound to danger signals and facilitated antigenic cross-presentation by DCs, significantly enhancing T cell activation and function. Experimental results showed that OH2-FLT3L significantly increased the proportion of activated DCs, enhanced the antitumor immune response, and effectively converted "cold" tumors into "hot" tumors. In addition, when combined with anti-PD-1 antibody, OH2-FLT3L further enhanced therapeutic efficacy. In conclusion, OH2-FLT3L, as a novel oncolytic virus, demonstrates the potential to enhance antitumor immune responses through DC activation.