Systemic Delivery of Oncolytic Viruses: Hopes and Hurdles

Abstract

<jats:p>Despite recent advances in both surgery and chemoradiotherapy, mortality rates for advanced cancer remain high. There is a pressing need for novel therapeutic strategies; one option is systemic oncolytic viral therapy. Intravenous administration affords the opportunity to treat both the primary tumour and any metastatic deposits simultaneously. Data from clinical trials have shown that oncolytic viruses can be systemically delivered safely with limited toxicity but the results are equivocal in terms of efficacy, particularly when delivered with adjuvant chemotherapy. A key reason for this is the rapid clearance of the viruses from the circulation before they reach their targets. This phenomenon is mainly mediated through neutralising antibodies, complement activation, antiviral cytokines, and tissue-resident macrophages, as well as nonspecific uptake by other tissues such as the lung, liver and spleen, and suboptimal viral escape from the vascular compartment. A range of methods have been reported in the literature, which are designed to overcome these hurdles in preclinical models. In this paper, the potential advantages of, and obstacles to, successful systemic delivery of oncolytic viruses are discussed. The next stage of development will be the commencement of clinical trials combining these novel approaches for overcoming the barriers with systemically delivered oncolytic viruses.</jats:p>

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part IV: Image- Guided, Remote-Controlled Opening of the Blood–Brain Barrier for Systemic Brain Tumor Therapy

“…The accumulation of effective concentrations of nanoparticles within GBM tissue could be increased using a stem cell-based strategy to bypass the BBB (37,38). The efficiency and safety of delivering GBM-targeted oncolytic viruses have also been enhanced using tumor-tropic stem cells (39,40). Thus, it has been established that using engineered stem cells to secrete therapeutics after migrating to tumor sites has strong therapeutic potential.…”

Evolution of Reovirus in Cancer Therapy

“…In particular, systemic delivery increases the probability that the virus can reach metastatic tumors or tumors that constitute multiple nodules that are not confined to a particular area. Unfortunately, various host factors, programmed to restrict the spread of pathogens, such as NARAs, nonspecific uptake by organs (spleen, lung, and liver) and scavenging immune cells, and poor virus escape from the vascular compartment, [96,97] significantly affect virus delivery through systemic routes. As reviewed by Roy et al, multiple steps have been attempted to ameliorate the systemic delivery of OVs with the use of cell carriers.…”

Vaccinia Virus, a Promising New Therapeutic Agent for Pancreatic Cancer

“…One such virus (JX594) has recently been shown to effectively target tumors after intravenous infusion, making it an ideal OV for treatment of inaccessible tumors such future science group Review Al Yaghchi, Zhang, Alusi, Lemoine & Wang as pancreatic cancer [7]. To date, the systemic delivery of OVs has been shown to be safe but not efficacious mainly due to the rapid clearance of these agents by the immune system [109]. When designing new strategy to enhance the systemic delivery of VV lessons can be learnt from other OVs.…”