Antitumor power of oncolytic HSV engineered with IL-12 and IL-15

Oncolytic herpes simplex virus type 1 (HSV-1) directly targets and destroys tumor cells while selectively infecting surrounding tumor tissue and releasing progeny viruses to continue the attack. We engineered the replicative HSV-1 vector, including the oncolytic HSV-1 (oHSV) with deleted inverted repeat and α47 gene, and then the oHSV expressing interleukin-15 (IL-15) gene and the oHSV expressing IL-15 and interleukin-12 (IL-12) gene. We evaluated the titer and growth characteristics of the oHSV-1 in Vero and cancer cell lines. Furthermore, we rigorously assessed the antitumor efficacy of HSV-1 in CT26 and B16-F10 cells, along with murine tumor models. The engineered oHSV-1 demonstrated growth patterns comparable to wild-type HSV-1. The viral titers exhibited consistency within the same tumor cells. Treatment with RG2006 significantly reduced tumor growth and extended survival rates compared to other forms of oHSV-1. Analyses indicated a marked elevation in T cell and NK cell activation in mice receiving RG2006. Our findings unequivocally demonstrate that including IL-15 and IL-12 can significantly enhance antitumor immunity when deploying oncolytic herpes simplex virus. This has substantial practical implications, suggesting that integrating multiple therapeutic genes alongside oncolytic viral therapy and immunotherapy could pave the way for more effective clinical strategies in cancer treatment.