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Updated: Jan 9, 2026
Intranasal Delivery of Therapeutic Stem Cells to Glioblastoma in a Mouse Model
Published on: June 4, 2017
An oncolytic herpesvirus expressing a CXCR4 antagonist interferes with glioblastoma cells' stemness features and
D'arrigo Paolo1, Dubois Maxime1, Sanchez Gil Judit1
1Laboratory of Virology and Immunology, GIGA-Immunobiology, University of Liège, 4000 Liège, Belgium.
Abstract:
Glioblastoma (GBM) is one of the most aggressive brain tumors. Despite the standard therapy, the survival from diagnosis remains dramatically low, especially due to tumor recurrence. Glioblastoma stem-like cells (GSCs) have been implicated in this tumor relapse, e.g., based on their capacity to escape the tumor and to migrate through the brain via CXCR4-dependent mechanisms. CXCR4 regulates biological features associated with tumor progression, including self-renewal, migration, and radio resistance. Importantly, its expression correlates with severity and poor prognosis of several cancers including GBM. The CXCR4/CXCL12 pathway therefore appears as an interesting potential therapeutic target. We have generated an oncolytic herpes simplex virus (oHSV) expressing HA-P2G, a mutated form of CXCL12 previously described as a CXCR4 competitive inhibitor. We demonstrate that, in vitro, oHSV/P2G impairs human GSC stemness marker expression, self-renewal, and migration. In two orthotopic xenograft murine models, oHSV/P2G intratumor injection limits tumor growth through the brain parenchyma and GSC migration through the corpus callosum. The ability of P2G to interfere with major GSC features demonstrates the interest in considering oHSV/P2G as a promising new therapeutic approach for GBM patients.
Insights
A novel oncolytic virus therapy (oHSV/P2G) targeting the CXCR4 pathway shows promise for glioblastoma (GBM). This treatment effectively inhibits glioblastoma stem-like cell (GSC) growth and migration, offering a potential new strategy against this aggressive brain cancer.
Area of Science:
- Neuro-oncology
- Virology
- Cancer Biology
Background:
- Glioblastoma (GBM) is a highly aggressive brain tumor with poor patient survival due to frequent recurrence.
- Glioblastoma stem-like cells (GSCs) drive tumor relapse by escaping the primary tumor and migrating through the brain.
- The CXCR4 receptor and its ligand CXCL12 play critical roles in GSC self-renewal, migration, and radioresistance, making the CXCR4/CXCL12 pathway a potential therapeutic target.
Purpose of the Study:
- To develop and evaluate an oncolytic herpes simplex virus (oHSV) expressing a CXCR4 inhibitor (HA-P2G) as a novel therapeutic agent for GBM.
- To assess the efficacy of oHSV/P2G in inhibiting GSC stemness, self-renewal, and migration in vitro.
- To determine the therapeutic potential of oHSV/P2G in reducing tumor growth and GSC dissemination in preclinical GBM models.
Main Methods:
- Generation of an oncolytic herpes simplex virus (oHSV) engineered to express HA-P2G, a mutated CXCL12 acting as a CXCR4 competitive inhibitor.
- In vitro assessment of oHSV/P2G's effects on human GSC stemness markers, self-renewal capacity, and migratory behavior.
- Intratumoral injection of oHSV/P2G in orthotopic xenograft murine models of GBM to evaluate tumor growth inhibition and GSC migration patterns.
Main Results:
- In vitro studies demonstrated that oHSV/P2G significantly impairs GSC stemness marker expression, reduces self-renewal, and inhibits migration.
- Intratumoral administration of oHSV/P2G in murine GBM models effectively limited tumor growth within the brain parenchyma.
- oHSV/P2G treatment also restricted GSC migration along the corpus callosum in vivo.
Conclusions:
- The engineered oncolytic virus oHSV/P2G effectively targets key glioblastoma stem-like cell (GSC) features, including stemness, self-renewal, and migration.
- The ability of P2G to interfere with GSC biology highlights its therapeutic potential.
- oHSV/P2G represents a promising novel therapeutic approach for glioblastoma patients, addressing tumor recurrence and progression.
