Ki67-targeted oncolytic adenovirus expressing IL-15 improves intratumoral T cell infiltration and PD-L1 expression in glioblastoma

Glioblastoma (GBM) is a devastating malignant brain tumor. Current therapeutic strategies targeting tumor cells have limited efficacy owing to the immunosuppressive microenvironment. Previous work demonstrated that the targeted Ad5-Ki67/IL-15 could specifically kill tumor cells and decrease the angiogenic capacity in vitro. However, the efficacy of this virus in vivo and its effect on the tumor microenvironment (TME) has not been elucidated. In this study, we found that the Ad5-Ki67/IL-15 treatment down-regulated PD-L1 expression of glioma cells. More importantly, Ad5-Ki67/IL-15 also remodeled the tumor microenvironment via increasing intratumoral T cell infiltration and PD-L1 improvement in a GBM model, as well as the increase of antitumor cytokines, thereby improving the efficacy of GBM treatment. Furthermore, a combination of Ad5-Ki67/IL-15 with PD-L1 blockade significantly inhibits tumor growth in the GBM model. These results provide new insight into the therapeutic effects of targeted oncolytic Ad5-Ki67/IL-15 in patients with GBM, indicating potential clinical applications.

Automated summary

In this study, the targeted oncolytic virus Ad5-Ki67/IL-15 was found to effectively down-regulate PD-L1 expression, remodel the tumor microenvironment, and increase the efficacy of GBM treatment. The combination of Ad5-Ki67/IL-15 with PD-L1 blockade further inhibits tumor growth.