oHSV-P10 Reduces Glioma Stem Cell Enrichment After Oncolytic HSV Therapy

Authors

Upasana Sahu
Matthew P Mullarkey
Guangsheng Pei
Zhongming Zhao
Bangxing Hong
Balveen Kaur

Publication Date

6-15-2023

Journal

Molecular Therapy Oncolytics

Abstract

Longstanding evidence implicate glioma stem-like cells as the main drivers contributing toward glioblastoma (GBM) therapy resistance and tumor recurrence. Although oncolytic herpes simplex virus (oHSV) viral therapy is a promising biological therapy recently approved for melanoma (in the United States and Europe) and GBM (in Japan); however, the impact of this therapy on GBM stem-like cells (GSCs) is understudied. Here we show that post-oHSV virotherapy activated AKT signaling results in an enrichment of GSC signatures in glioma, which mimics the enrichment in GSC observed after radiation treatment. We also uncovered that a second-generation oncolytic virus armed with PTEN-L (oHSV-P10) decreases this by moderating IL6/JAK/STAT3 signaling. This ability was retained in the presence of radiation treatment and oHSV-P10-sensitized intracranial GBM to radiotherapy. Collectively, our findings uncover potential mechanisms to overcome GSC-mediated radiation resistance via oHSV-P10.

Keywords

MT: Regular Issue, glioblastoma, oncolytic HSV1, glioma stem cells, IL6, STAT3, irradiation

DOI

10.1016/j.omto.2023.03.003

PMID

37114074

PMCID

PMC10126842

PubMedCentral® Posted Date

4-3-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes