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

Virology

Brain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China; Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, 100070, China; Beijing Laboratory of Biomedical Materials, Beijing, 100070, China. Electronic address:

Published: October 2023

AI Article Synopsis

  • Glioblastoma (GBM) is a really bad type of brain tumor that's hard to treat.
  • Researchers tested a special virus called Ad5-Ki67/IL-15 that can kill tumor cells and change the area around the tumor to help the immune system fight back.
  • They found that this treatment helps increase good immune cells in the tumor, lowers a blocker called PD-L1, and works even better when combined with another therapy, which could lead to new ways to help patients with GBM.

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/j.virol.2023.109885DOI Listing

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