Abstract
Oncolytic viruses (OVs) have been used in the treatment of cancer, in a focused manner, since the 1990s. These OVs have become popular in the treatment of several cancers but are only now gaining interest in the treatment of glioblastoma (GBM) in recent clinical trials. In this review, the authors discuss the unique applications of intraarterial (IA) delivery of OVs, starting with concepts of OV, how they apply to IA delivery, and concluding with discussion of the current ongoing trials. Several OVs have been used in the treatment of GBM, including specifically several modified adenoviruses. IA delivery of OVs has been performed in the hepatic circulation and is now being studied in the cerebral circulation to help enhance delivery and specificity. There are some interesting synergies with immunotherapy and IA delivery of OVs. Some of the shortcomings are discussed, specifically the systemic response to OVs and feasibility of treatment. Future studies can be performed in the preclinical setting to identify the ideal candidates for translation into clinical trials, as well as the nuances of this novel delivery method.
Highlights
Oncolytic viruses (OVs) have been tested since the 1950s;1–3 it was not until the 1990s1 that viral genomic engineering resulted in the first generation of cancer-selective therapeutic OVs.[4]
We will discuss the unique applications of IA delivery of OVs, starting with concepts of OV, how they apply to IA delivery, and concluding with discussion of the current ongoing trials
It developed from the initial open surgical carotid infusion of triethylenemelamine nitrogen mustard, to endovascular infusion of melphalan (l-phenylalanine mustard)[23] into the internal carotid artery (ICA) with distal balloon occlusion, to direct catheterization and infusion[24] of melphalan, carboplatin, and topotecan through the ophthalmic artery, with a reported 92% ocular survival in 452 eyes.[25]
Summary
Oncolytic viruses (OVs) have been used in the treatment of cancer, in a focused manner, since the 1990s. There are several OVs that have been studied for their potential in the treatment of GBM This has included several types of OVs (for example, adenovirus,[7] Newcastle disease virus,[7] vaccinia virus,[7] and herpes simplex virus [HSV]8), combinations thereof, and modified viruses such as the replication-deficient adenoviruses (e.g., AdV-tk[4]). The agent that has advanced the furthest in clinical trials far has been Delta-24-RGD, which was the first clinical study to show direct oncolysis and replication of a therapeutic adenovirus in human brain tumors and to provide correlative evidence for a viral-induced antiglioma immune response.[14] Since further trials have continued and have been partially reported on with Delta24-RGD.[15]. While recent studies of gene therapy for GBM have been lacking, new delivery methods such as endovascular selective intraarterial (ESIA) may be considered
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