Tumor-targeting oncolytic HSV-SUR15 enhances anti-tumor immunity in glioblastoma

Glioblastoma (GBM) is the most prevalent and aggressive primary brain tumor, and remains a major unmet medical need for most patients on the standard treatment regimen. Recently, clinical trial results using engineered oncolytic herpes simplex virus (oHSV) have illuminated the potential of oncolytic therapy in GBM but have also shown limited success. Here, we report a novel oncolytic herpes simplex virus HSV-SUR15, that may offer a promising treatment strategy for GBM. HSV-SUR15 utilizes a tumor-specific survivin promoter to restore the viral neurovirulence ICP34.5 gene and ribonucleotide reductase ICP6 gene, enhancing viral replication and cytotoxicity specifically in tumor cells. Simultaneously, HSV-SUR15 can also activate T cells and natural killer (NK) cells by secreting interleukin-15 (IL-15). We found that this combination strategy synergistically enhanced the ability of oHSV to establish durable tumor-specific immune responses, and effectively suppressed tumor growth in mouse models of glioblastoma. Our study effectively overcomes the inherent limitations of oHSV and IL-15 monotherapy, providing valuable insights for the clinical treatment of GBM.