oncolytic herpes simplex virus expressing FLT3 ligand + OX40 ligand + interleukin-12

This engineered next-generation oncolytic herpes simplex virus (oHSV) is designed to express three potent immunomodulatory transgenes: FLT3 ligand (FLT3L), OX40 ligand (OX40L), and interleukin-12 (IL-12). The virus selectively replicates within and lyses tumor cells, releasing these factors into the tumor microenvironment to stimulate a multi-pronged antitumor immune response. FLT3L promotes the recruitment and maturation of dendritic cells (DCs); OX40L provides essential co-stimulatory signals to T cells; and IL-12 enhances Th1 polarization and cytotoxic T-cell activity. Research indicates that this triple-transgene construct can effectively reverse immunosuppressive circuits, such as the monocyte-CAF-DC axis, which typically restricts the efficacy of immunotherapy in dense desmoplastic tumors like pancreatic ductal adenocarcinoma (PDAC).