DN146

DN146 is an engineered oncolytic herpes simplex virus (oHSV) designed to selectively infect and lyse tumor cells while stimulating a robust systemic antitumor immune response. The virus features a re-engineered gamma 1 34.5 gene, which preserves efficient viral replication and cytotoxicity while promoting the activation of the STING (Stimulator of Interferon Genes) and RIG-I (Retinoic Acid-Inducible Gene I) innate immune sensing pathways. Additionally, DN146 is armed with a transgene encoding a high-affinity SIRPalpha (Signal Regulatory Protein Alpha) decoy. This decoy protein antagonizes the CD47-SIRPalpha immune checkpoint, thereby enhancing macrophage-mediated phagocytosis of tumor cells and facilitating T-cell recruitment and antigen cross-presentation. Preclinical studies in murine models of triple-negative breast cancer and colorectal cancer have demonstrated that DN146 can induce the clearance of both injected primary tumors and distal metastatic lesions, suggesting potential for systemic efficacy.