Mesenchymal stromal cells for the delivery of oncolytic viruses in gliomas

Abstract

Mesenchymal stromal cells (MSCs) are a type of adult stem cell that has been exploited for the treatment of a variety of diseases, including cancer. In particular, MSCs have been studied extensively for their ability to treat glioblastoma (GBM), the most common and deadly form of brain cancer in adults. MSCs are attractive therapeutics because they can be obtained relatively easily from patients, are capable of being expanded numerically in vitro, can be easily engineered and are inherently capable of homing to tumors, making them ideal vehicles for delivering biological antitumoral agents. Oncolytic viruses are promising biological therapeutic agents that have been used in the treatment of GBMs, and MSCs are currently being explored as a means of delivering these viruses. Here we review the role of MSCs in the treatment of GBMs, focusing on the intersection of MSCs and oncolytic viruses.

Keywords: adenovirus; gliomas; mesenchymal stem cell; mesenchymal stromal cell.

Figure 1

Delta-24-RGD harbors a 24-base pair deletion in the viral E1A region that is responsible for binding Retinoblastoma (Rb), and contains the inserted RGD sequence to enhance infectivity (Figure 1A). Rb protein normally prevents cells from entering S-phase. Because E1A is mutated, the virus is unable to replicate in cells that have functioning Rb, i.e. normal cells. However, the virus is able to replicate in cells that have lost or mutated Rb protein, i.e. tumor cells (Figure 1B).