Anti-tumor efficacy of oncolytic herpes simplex viruses constructed by synthetic genomics in a murine colorectal carcinoma model and in human tumor cell lines.

Colorectal cancer (CRC) is one of the most common malignancies globally and effective therapeutic strategies are essential. Oncolytic viruses present a promising therapeutic strategy in this regard. In a previous study, we synthesized two oncolytic herpes simplex virus type I (oHSV-1), oHSV-1.1, and oHSV-1.2. Both viruses were attenuated by deleting the virulence genes ICP34.5 and ICP47, while oHSV-1.2 was further armed with murine granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-12 (IL-12) for immune activation. Both viruses exhibit significant anti-tumor efficacy in a murine melanoma model. In the present study, we evaluated the oncolytic potential of oHSV-1.1 and oHSV-1.2, in an immunocompetent murine CRC model and in human tumor cell lines. oHSV-1.2 induced significant tumor inhibition and anti-tumor activity in vivo, as evidenced by tumor regression, enhanced neutrophil infiltration, activation of specific anti-tumor immune responses, and significant pathological damage in tumor tissue. Additionally, both oHSV-1.1 and oHSV-1.2 replicated and exerted cytotoxicity in various human tumor cells in vitro. This study provides valuable insights into the application of oHSV-1.2 for the treatment of CRC.