Locoregional intravascular viral therapy of cancer: precision guidance for Paris's arrow?

Abstract

Viral therapy of cancer includes strategies such as viral transduction of tumour cells with ‘suicide genes’, using viral infection to trigger immune-mediated tumour cell death and using oncolytic viruses for their direct anti-tumour action. However, problems still remain in terms of adequate viral delivery to tumours. A role is also emerging for single-organ isolation and perfusion. Having begun with the advent of isolated limb perfusion for extremity malignancy, experimental systems have been developed for the perfusion of other organs, particularly the liver, kidneys and lungs. These are beginning to be adopted into clinical treatment pathways. The combination of these two modalities is potentially significant. Locoregional perfusion increases the exposure of tumour cells to viral agents. In addition, the avoidance of systemic elimination through the immune and reticulo-endothelial systems should provide a mechanism for increased transduction/infection of target cells. The translation of laboratory research to clinical practice would occur within the context of perfusion programmes, which are already established in the clinic. Many of these programmes include the use of vasoactive cytokines such as tumour necrosis factor-α, which may have an effect on viral uptake. Evidence of activation of specific antitumour immunological responses by intratumoural and other existing methods of viral administration raises the intriguing possibility of a locoregional therapy, with the ability to affect distant sites of disease. In this review, we examined the state of the literature in this area and summarized current findings before indicating likely areas of continuing interest.

Isolated limb perfusion with melphalan, tumour necrosis factor‐alpha and oncolytic vaccinia virus improves tumour targeting and prolongs survival in a rat model of advanced extremity sarcoma

“…The systemic toxicity of TNF‐α prevents administration other than by ILP. Finally, an existing network of established clinical ILP programmes may facilitate translation into early‐phase clinical trials in this surgically challenging patient group . Recent data on the combination of ILP with oncolytic viral therapy, and evidence of efficacy against human sarcoma and melanoma cell lines, supports further investigation of this approach.…”

Interventional oncology: A snapshot of expanding practice

“…[3] To overcome such limitations and ameliorate the toxicities of systemic delivery, other locoregional delivery routes have been considered to optimize the delivery of oncolytic viruses including intraarterial, intratumoral, and intracavitary routes in addition to organ isolation/perfusion. [9] However, these routes still lead to systemic spread of amplified virus that enters the bloodstream from the lytic tumor cells, resulting in abscopal effect with infection of distance metastases. These locoregional delivery routes have been paid attention to the potential of interventional radiology techniques for facilitating such delivery using different interventional techniques under imaging guidance.…”

Addressing the Donor Liver Shortage with EX VIVO Machine Perfusion

“…Defatting of steatotic organs is currently being attempted using perfusate compositions that increase the catabolism of lipids and improve microcirculation with vasodilators [20][21][22]. Perfusate is specific to treatment of liver tumors [23,24], inoculation of donor organs against further viral damage upon transplantation into hepatitis-positive recipients [25,26], and preconditioning donor organs to better tolerate downstream ischemia [27].…”