Oncolytic viruses as experimental treatments for malignant gliomas: Using a scourge to treat a devil

Abstract 

The concept of oncolytic viral therapy has a century-old history, but only within the last 20 years have oncolytic viruses been considered for the treatment of brain cancers. Viruses such as herpes, measles, and vaccinia have all been known to cause devastating cases of neurological disease in humans, yet these ‘scourges’ are now being harnessed in such a way that they prove very useful as cancer therapeutics. There have been 8 formal clinical trials and 3 case studies using oncolytic viruses to treat malignant glioma patients. Although some success has been reached with oncolytic therapy, overall it has fallen short of expectations. In this review we analyze the results of these trials and bring to light some of the limitations and pitfalls of this therapy, as well as present some promising preclinical work that has been proposed to circumvent such problems.

Abbreviations: AdV, Adenovirus, APC, antigen-presenting cell, BBB, blood–brain barrier, CED, convection-enhanced delivery, CNS, central nervous system, ECM, extracellular matrix, FasL, Fas ligand, GALV, gibbon ape leukemia virus, GBM, glioblastoma mulitforme, GIM, glioma-infiltrating macrophage/microglia, GII, glioma-infiltrating immunocytes, GR, glucocorticoid receptors, HSV-1, Herpes Simplex Virus, IFN, interferon, i.t., intratumoral, i.v., intravenous, MG, malignant glioma, MTD, maximum tolerated dose, MV, Measles virus, MYXV, Myxoma virus, NDV, Newcastle Disease Virus, OV, oncolytic virus, PAMP, pathogen-associated molecular pattern, PRR, pathogen recognition receptor, PV, Poliovirus, RT, radiation therapy, RV, Reovirus, SAS, sub-archanoid space, TBK, TANK-binding kinase 1, T_reg, regulatory T-cell, VRS, Virchow–Robin space, VV, Vaccinia virus

Keywords: Glioma, Oncolytic virus, Clinical trials, Neuroimmunology, Neurovirulence, Viral delivery, Brain tumor-initiating cells, Synergizing treatments