Strategies to Optimise Oncolytic Viral Therapies: The Role of Natural Killer Cells

Oncolytic viruses (OVs) are an emerging class of anti-cancer agents that replicate selectively within malignant cells and generate potent immune responses. Their potential efficacy has been shown in clinical trials, with talimogene laherparepvec (T-VEC or IMLYGIC((R))) now approved both in the United States and Europe. In healthy individuals, NK cells provide effective surveillance against cancer and viral infections. In oncolytic viral therapy, NK cells may render OV ineffective by rapid elimination of the propagating virus but could also improve therapeutic efficacy by preferential killing of OV-infected malignant cells. Existing evidence suggests that the overall effect of NK cells against OV is context dependent. In the past decade, the understanding of cancer and OV biology has improved significantly, which helped refine this class of treatments in early-phase clinical trials. In this review, we summarised different strategies that have been evaluated to modulate NK activities for improving OV therapeutic benefits. Further development of OVs will require a systematic approach to overcome the challenges of the production and delivery of complex gene and cell-based therapies in clinical settings.