A Recombinant Oncolytic Pseudorabies Virus Expressing Interleukin-18, Interferon-Gamma and PH20 Genes Promotes Systemic Antitumor Immunity

Pseudorabies virus (PRV) is considered to be a promising oncolytic virus that has potential as a cancer gene therapy drug. In this study, PRV-DCD-1-70 was used as a vector to carry exogenous genes IL-18, IFN-? and PH20 to construct novel recombinant PRV, rPRV-PH20 and rPRV-IL-18-?-PH20, and their tumorolytic effects were evaluated in vitro and in vivo. Our study showed that recombinant PRV lysed all four tumor cell lines, Pan02, EMT-6, CT26 and H446, and rPRV-IL-18-?-PH20 showed the best tumor lysis effect. Further studies in mice bearing Pan02 tumors showed that recombinant PRV, especially rPRV-IL-18-?-PH20, were able to inhibit tumor growth. Moreover, an immunohistochemical analysis indicated that the recombinant PRV effectively increased the infiltration of CD4(+)T and CD8(+)T cells and enhanced the anti-tumor immune response of the organism in vivo. Overall, PRV carrying PH20 and IL-18-? exogenous genes demonstrated anti-tumor effects, providing a foundation for the further development and application of PRV as a novel tumor oncolytic virus vector.

Automated summary

In this study, a recombinant pseudorabies virus (PRV) carrying exogenous IL-18, IFN-?, and PH20 genes was constructed and evaluated for its tumorolytic effects. The results showed that the recombinant PRV effectively lysed tumor cells and inhibited tumor growth in mice. Immunohistochemical analysis demonstrated enhanced anti-tumor immune response in vivo. This study provides a foundation for further development and application of PRV as a novel tumor oncolytic virus vector.