Glioblastoma Therapy: Rationale for a Mesenchymal Stem Cell-based Vehicle to Carry Recombinant Viruses

Abstract

Evasion of growth suppression is among the prominent hallmarks of cancer. Phosphatase and tensin homolog (PTEN) and p53 tumor-suppressive pathways are compromised in most human cancers, including glioblastoma (GB). Hence, these signaling pathways are an ideal point of focus for novel cancer therapeutics. Recombinant viruses can selectivity kill cancer cells and carry therapeutic genes to tumors. Specifically, oncolytic viruses (OV) have been successfully employed for gene delivery in GB animal models and showed potential to neutralize immunosuppression at the tumor site. However, the associated systemic immunogenicity, inefficient transduction of GB cells, and inadequate distribution to metastatic tumors have been the major bottlenecks in clinical studies. Mesenchymal stem cells (MSCs), with tumor-tropic properties and immune privilege, can improve OVs targeting. Remarkably, combining the two approaches can address their individual issues. Herein, we summarize findings to advocate the reactivation of tumor suppressors p53 and PTEN in GB treatment and use MSCs as a "Trojan horse" to carry oncolytic viral cargo to disseminated tumor beds. The integration of MSCs and OVs can emerge as the new paradigm in cancer treatment.

Keywords: Mesenchymal stem cells; Oncolytic viruses; Targeted delivery; Tumor suppressors.