Oncolytic Viral Therapy of Malignant Glioma

Abstract

SUMMARY Novel approaches to treatment of malignant glioma, the most frequently occurring primary brain tumor, have included the use of a wide range of oncolytic viral vectors. These vectors, either naturally tumor-selective, or engineered as such, have shown promise in the handful of Phase I and Phase II clinical trials conducted in recent years. The strategies developed for each of the different viruses currently being studied, and the history of their development, are summarized here. Additionally, the results of clinical trials in patients, and their implication for future trials, are also discussed.

Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1

“…2 As most tumor recurrences are within the initial tumor bed, direct injection of attenuated oncolytic viruses such as herpes simplex virus-1 (HSV-1) has been proposed as an adjuvant treatment and utilized in Phase I clinical trials for high-grade gliomas. [3][4][5][6][7] HSV-1 is a double-stranded DNA virus expressing its genes in a sequential cascade of immediate-early (a), early (b), and late (g) genes. 8 Immediate-early genes encode for viral transcriptional regulators.…”

“…Oncolytic viruses have been genetically engineered by deleting specific viral genes in order to restrict viral replication to cancer cells and also attenuate virulence to increase patient safety. 7,9 A major strategy has focused on deleting the g 1 34.5 late gene of HSV-1, which in part mediates neurovirulence. 10 Phase I clinical trials in patients with glioma have been completed with neuro-attenuated HSV-1 deleted of g 1 34.5 that have demonstrated the safety and feasibility of this approach.…”

Genetic and Immunology of Brain Tumors

“…The most common vectors are replicating herpes simplex virus (HSV), adenovirus and replication-competent retrovirus (RCR). Replicating herpes simplex virus (HSV) vectors have been tested for the treatment of malignant glioma (Grandi et al, 2009;Granelli-Piperno et al, 2000;Parker et al, 2009). The common widely studied oncolytic HSV vector is G207, a genetically engineered HSV-1 (Markert et al, 2000).…”

Targeted Therapy for Gliomas: the Oncolytic Virus Applications

“…Some of the oncolytic virus been studied and reported in phase 1 against glioma are the herpes simplex virus (HSV), adenovirus, reovirus, and NDV, while the measles virus, vaccinia virus, myxoma virus, polio virus, and vesicular stomatitis virus were at the preclinical level. (Parker et al, 2009) For NDV, the strain been studied on glioma are the MTH/68H, NDV-HUJ,OV-001, 73-T and V4UPM. The V4UPM is the avirulent strain o f N D v i r u s t h a t h a s b e e n u s e d a s a thermostable feed pellet vaccine for poultry.…”