Although oncolytic herpes simplex virus (HSV) has been found to be safe in clinical trials in malignant glioblastoma multiforme, its efficacy is limited by insufficient viral spread after tumor resection. In a study reported in the Journal of the National Cancer Institute, Duebgen and colleagues showed that loading of human mesenchymal stem cells with multimechanistic oncolytic HSV variants represents a promising approach in treatment of glioblastoma multiforme.
Mesenchymal stem cell–oncolytic HSVs successfully produced oncolytic HSV progeny, resulting in killing of glioblastoma multiforme cells in vitro and in vivo. Mesenchymal stem cell–oncolytic HSVs encapsulated in biocompatible synthetic extracellular matrix produced a significant increase in anti–glioblastoma multiforme efficacy compared with direct injection of purified oncolytic HSV in a mouse model of glioblastoma multiforme resection, resulting in prolonged median survival (P < .001). In a model of resistant tumors, mesenchymal stem cells loaded with the proapoptotic variant oncolytic HSV–TRAIL induced apoptosis-mediated killing and prolonged median survival in mice with oncolytic HSV– and TRAIL-resistant glioblastoma multiforme (P < .001).
The investigators concluded, “Human [mesenchymal stem cells] loaded with different [oncolytic] HSV variants provide a platform to translate oncolytic virus therapies to clinics in a broad spectrum of [glioblastoma multiforme] after resection and could also have direct implications in different cancer types.” ■
Duebgen M, et al: J Natl Cancer Inst 106:dju090, 2014.