Intraarterial delivery of virotherapy for glioblastoma

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.

Oncolytic Viruses for Malignant Glioma: On the Verge of Success?

“…BM-hMSCs are known to show natural tropism for human gliomas, which facilitates the homing of DNX-2401-loaded BM-hMSCs to glioma tumors [ 94 ]. Furthermore, this study used the endovascular selective intra-arterial administration (ESIA) technique that facilitates localized delivery of BM-hMSCs to glioma tumors by disrupting the BBB using hyperosmotic solution (as reviewed in [ 95 , 96 ]). NSCs loaded with CRAd-survivin-pk7 will be delivered directly into tumors with the goal of enhancing virus spread within the tumor.…”

Oncolytic virus in gliomas: a review of human clinical investigations

“…While CED provides positive pressure, backflow can limit the distribution to the tumor edge and infiltrating tumor cells, which is the area most difficult to resect and achieve tumor control. 62 It is these distant cells, however, that are the likely source of recurrence and most desperately need tumor control which CED appears to provide. Systemic therapy, including both i.v.…”

“…Nevertheless, intravascular OV therapy continues to be a promising avenue of investigation given the potential to enhance OV spread throughout the tumor, including the periphery and distant tumor cells. 62 To overcome these challenges associated with intravascular OV delivery, methods of circumventing the BBB and neutralizing antibodies have been recently explored: mannitol infusions, focused ultrasound, and microbubble-mediated drug delivery systems are under active investigation. [62][63][64] Further modifying OVs either by genetic or chemical means is an active area of further investigation.…”

“…62 To overcome these challenges associated with intravascular OV delivery, methods of circumventing the BBB and neutralizing antibodies have been recently explored: mannitol infusions, focused ultrasound, and microbubble-mediated drug delivery systems are under active investigation. [62][63][64] Further modifying OVs either by genetic or chemical means is an active area of further investigation. 9 A recent report cites production of a recombinant measles virus with modifications that maintain oncolytic activity while evading anti-measles antibodies.…”

Oncolytic Virotherapy for Melanoma Brain Metastases, a Potential New Treatment Paradigm?

“…Here, immunotherapy may work synergistically with virotherapy, enhancing the immune response to infected tumor cells. Further work exploring intra-arterial delivery of oncolytic viruses is ongoing [80].…”