Abstract
The concept of oncolytic viral therapy was based on the hypothesis that engineering tumor-selectivity into the replication potential of viruses would permit direct destruction of tumor cells as a result of viral-mediated lysis, resulting in amplification of the therapy exclusively within the tumor environment. The immune response raised by the virus was not only considered to be necessary for the safety of the approach, but also something of a hindrance to optimal therapeutic activity and repeat dosing. However, the pre-clinical and subsequent clinical success of several oncolytic viruses expressing selected cytokines has demonstrated the potential for harnessing the immune response as an additional and beneficial mechanism of therapeutic activity within the platform. Over the last few years, a variety of novel approaches have been incorporated to try to enhance this immunotherapeutic activity. Several innovative and subtle approaches have moved far beyond the expression of a single cytokine transgene, with the hope of optimizing anti-tumor immunity while having minimal detrimental impact on viral oncolytic activity.
Highlights
Viral infections and cancer bear a variety of striking similarities, as seen with the fact that several cancers are caused as a result of chronic viral infection [1, 2] and the fact that the first oncogenes were identified through their homology to viral genes [3, 4]
There is clearly a fine balance to be considered as robust induction of the immune response can lead to premature clearance of the therapy, meaning that the oncolytic effects are lost and adaptive immunity is targeted against the viral component only, with little or no cross-presentation of tumor antigens
Several vaccinia and related vectors expressing single cytokines have clearly demonstrated therapeutic benefits in both animal models and in the clinic, this approach typically suffers from several handicaps, including reduced viral replication due to reduced initial infection of the tumor or early clearance of the virus [32]; in addition, the use of a single cytokine means that typically only one step in the complex kinetic process of innate to adaptive immune response can be stimulated
Summary
Viral infections and cancer bear a variety of striking similarities, as seen with the fact that several cancers are caused as a result of chronic viral infection [1, 2] and the fact that the first oncogenes were identified through their homology to viral genes [3, 4]. There is clearly a fine balance to be considered as robust induction of the immune response can lead to premature clearance of the therapy, meaning that the oncolytic effects are lost and adaptive immunity is targeted against the viral component only, with little or no cross-presentation of tumor antigens.
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