**1. Oncolytic Virotherapy (OVT)**

Advancements in virology and molecular biology techniques over recent decades have allowed us to exploit the anti-tumour potential of oncolytic viruses (OVs) [1]. The unique ability of OVs to exploit oncogenic signalling pathways provides a significant advantage over traditional treatment modalities. OVs are specifically defined as viruses which: (i) preferentially infect and kill malignant cells through viral replication and oncolysis, and (ii) engage the immune system to promote anti-tumour immunity. Additional mechanisms of action have also been reported, including disruption of tumour-associated vasculature or stroma and modulation of the tumour microenvironment (TME) [2–4].

An array of OVs—naturally occurring, attenuated, and genetically modified—have been investigated in pre-clinical models and clinical trials but only two have received approval for clinical use: (i) a genetically engineered adenovirus H101, approved in China in 2005 [5], and (ii) the Food and Drug Administration (FDA)-approved talimogene laherparepvec (T-VEC)—a herpes simplex virus type 1 (HSV-1) genetically engineered to limit neurovirulence and promote an immunostimulatory environment [6,7]. This review will provide an overview of what we have learnt about oncolytic mammalian orthoreovirus since its rise as a clinically applicable agent, we will discuss areas of active pre-clinical and clinical research and consider the challenges that exist to harness its full therapeutic potential.
