Myxoma virus and oncolytic virotherapy: a new biologic weapon in the war against cancer

Abstract

Oncolytic virotherapy is an innovative alternative to more conventional cancer therapies. The ability of some viruses to specifically target and kill malignant cancerous cells while leaving normal tissue unscathed has opened a large repertoire of new and selective cancer killing therapeutic candidates. Poxviruses, such as vaccinia virus, have a long history of use in humans as live vaccines and have more recently been studied as potential platforms for delivery of immunotherapeutics and attenuated variants of vaccinia have been explored as oncolytic candidates. In contrast, the poxvirus myxoma virus is a novel oncolytic candidate that has no history of use in humans directly, as it has a distinct and absolute host species tropism to lagomorphs (rabbits). Myxoma virus has been recently shown to be able to also selectively infect and kill human tumor cells, a unique tropism that is linked to dysregulated intracellular signalling pathways found in the majority of human cancers. This review outlines the existing knowledge on the tropism of myxoma virus for human cancer cells, as well as preclinical data exhibiting its ability to infect and clear tumors in animal models of cancer. This is an exciting new therapeutic option for treating cancer, and myxoma virus joins a growing group of oncolytic virus candidates that are being developed as a new class of cancer therapies in man.

Keywords::

• Akt
• mTOR
• oncolysis
• poxvirus
• rapamycin
• virotherapy

Acknowledgements

GM was funded by the National Cancer Institute of Cancer and the Canadian Institute for Health Research, and is presently an International Scholar of the Howard Hughes Medical Institute. MMS is supported by a Postdoctoral Fellowship provided by the Pamela Greenaway Kohlmeier Translational Breast Cancer Research Unit of the London Regional Cancer Program. The authors would like to thank Dr J Barrett for helpful comments in manuscript preparation.

Disclosure

Myxoma virus has been licensed by the Robarts Research Institute to Wellstat Biologics.