Oncolytic Virus Therapy in a New Era of Immunotherapy, Enhanced by Combination with Existing Anticancer Therapies: Turn up the Heat!

Abstract

Oncolytic viral therapy is a promising treatment for cancer, where 'cold' tumour cells can become 'hot' to the host immune system. However, with few FDA approved therapies, development of new strategies for more cancer types has been slow and relatively unsuccessful in recent years, Combination therapy has been successful for other types of cancer treatment, therefore, may be a viable alternative to improve the efficacy of oncolytic viral therapy which may reduce some of the adverse events of currently used monotherapies, oncolytic virus therapy and chemotherapy being mutually complimentary with each other. Combining oncolytic viruses with immune checkpoint inhibitors provides a significant increase in efficacy when viral therapy was combined with the drug ipilimumab. Phase I and II studies concluded that combination with chemotherapies was safe and effective but did not significantly improve on current monotherapies. Recent experiments suggest that a combination of CAR-T and CAR--M cells is a promising therapeutic approach but needs to advance to clinical testing to observe the human response to the therapy. Viral combination with ipilimumab showed the highest potential for a successful treatment and clinical trials should be advanced to phase III to find conclusive supporting evidence. This review aims to identify and evaluate the potential of currently evolving oncolytic viral therapy with recent advances in genetic engineering providing enhanced oncolytic activity in the tumour, and addressing the lack of host immune responses in 'cold' tumours, with an additional role in enhancing conventional treatment efficacy with combination therapies. The potential of oncolytic viruses to 'turn up the heat' of a tumour microenvironment immunogenicity in combination with other anticancer treatments, provides a promising future for new cancer therapies.