To effectively build on the recent successes of immune checkpoint blockade, adoptive T cell therapy and cancer vaccines, it is critical to rationally design combination strategies that will increase and extend efficacy to a larger proportion of patients. For example, the combination of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and anti-programmed cell death protein 1 (PD1) immune checkpoint inhibitors essentially doubles the response rate in certain patients with metastatic melanoma. However, given the heterogeneity of cancer, it seems likely that even more complex combinations of immunomodulatory agents may be required to obtain consistent, durable therapeutic responses against a broad spectrum of cancers. This carries serious implications in terms of toxicities for patients, feasibility for care providers and costs for health-care systems. A compelling solution is offered by oncolytic viruses (OVs), which can be engineered to selectively replicate within and destroy tumour tissue while simultaneously augmenting antitumour immunity. In this Opinion article, we argue that the future of immunotherapy will include OVs that function as multiplexed immune-modulating platforms expressing factors such as immune checkpoint inhibitors, tumour antigens, cytokines and T cell engagers. We illustrate this concept by following the trials and tribulations of tumour-reactive T cells from their initial priming through to the execution of cytotoxic effector function in the tumour bed. We highlight the myriad opportunities for OVs to help overcome critical barriers in the T cell journey, leading to new synergistic mechanisms in the battle against cancer.
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K.T.-B. was supported by a postdoctoral fellowship from the Susan G. Komen Foundation. B.H.N. receives support from the British Columbia Cancer Foundation. J.C.B. and B.H.N. receive support from the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute and The Terry Fox Foundation. J.C.B. also receives funding from the Ontario Institute for Cancer Research.
Nature Reviews Cancer thanks A. Melcher and the other anonymous reviewer(s) for their contribution to the peer review of this work.
J.C.B. is co-founder of Turnstone Biologics, a paid consultant for Turnstone Biologics and on the Board of Directors for Turnstone Biologics. K.T.-B., J.L.P., Y.Y.E.K. and B.H.N. declare no competing interests.
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Twumasi-Boateng, K., Pettigrew, J.L., Kwok, Y.Y.E. et al. Oncolytic viruses as engineering platforms for combination immunotherapy. Nat Rev Cancer 18, 419–432 (2018). https://doi.org/10.1038/s41568-018-0009-4
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