Abstract
Reoviruses are non-enveloped viruses with a segmented double stranded RNA genome. In humans, they are not associated with serious disease. Human reoviruses exhibit an inherent preference to replicate in tumor cells, which makes them ideally suited for use in oncolytic virotherapies. Their use as anti-cancer agent has been evaluated in several clinical trials, which revealed that intra-tumoral and systemic delivery of reoviruses are well tolerated. Despite evidence of anti-tumor effects, the efficacy of reovirus in anti-cancer monotherapy needs to be further enhanced. The opportunity to treat both the primary tumor as well as metastases makes systemic delivery a preferred administration route. Several pre-clinical studies have been conducted to address the various hurdles connected to systemic delivery of reoviruses. The majority of those studies have been done in tumor-bearing immune-deficient murine models. This thwarts studies on the impact of the contribution of the immune system to the tumor cell eradication. This review focuses on key aspects of the reovirus/host-cell interactions and the methods that are available to modify the virus to alter these interactions. These aspects are discussed with a focus on improving the reovirus’ antitumor efficacy.
Highlights
The field of oncolytic virus therapy has evolved rapidly since the late 1990s as can be appreciated from the increase in publications on this topic (Figure 1)
This review focuses on the use of mammalian orthoreoviruses in oncolytic therapies, and on the various strategies that can be used to enhance their oncolytic potency
[3] Early on, researchers recognized their capacity to induce cell death in tumor cells, while normal, diploid cells are largely resisting reovirus infection. This observation was first noted in the late 1970s when human cell lines and cell lines from rat, mouse, and monkey origins were exposed to reovirus Type 2 [4]
Summary
The field of oncolytic virus therapy has evolved rapidly since the late 1990s as can be appreciated from the increase in publications on this topic (Figure 1). Reoviruses have been found in children with respiratory and gastrointestinal illnesses, their role remains unclear and there are no convincing data for a causal relation [3] Early on, researchers recognized their capacity to induce cell death in tumor cells, while normal, diploid cells are largely resisting reovirus infection. This observation was first noted in the late 1970s when human cell lines and cell lines from rat, mouse, and monkey origins were exposed to reovirus Type 2 [4].
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