Current understanding of reovirus oncolysis mechanisms

Abstract

Mammalian orthoreovirus (reovirus) is under development as a cancer virotherapy. Clinical trials demonstrate that reovirus-based therapies are safe and tolerated in patients with a wide variety of cancers. Although reovirus monotherapy has proven largely ineffective, reovirus sensitizes cancer cells to existing chemotherapeutic agents and radiation. Clinical trials are underway to test the efficacy of reovirus in combination with chemotherapeutic and radiation regimens and to evaluate the effectiveness of reovirus in conjunction with immunotherapies. Central to the use of reovirus to treat cancer is its capacity to directly kill cancer cells and alter the cellular environment to augment other therapies. Apoptotic cell death is a prominent mechanism of reovirus cancer cell killing. However, reoviruses can also kill cancer cells through nonapoptotic mechanisms. Here, we describe mechanisms of reovirus cancer cell killing, highlight how reovirus is used in combination with existing cancer treatments, and discuss what is known as to how reovirus modulates cancer immunotherapy.

Keywords:

• virotherapy
• cancer
• immunotherapy
• cell death
• interferon

Acknowledgments

This research was supported by Public Health Award R01 AI118801 (K.W.B.), Children’s Healthcare of Atlanta, the Emory Children’s Pediatric Center, and Winship Cancer Institute IRG-14-188-01 from the American Cancer Society (B.A.M.). Additional support was provided by the Center for Microbial Pathogenesis and Host Inflammatory Response (P20 GM103625).

Disclosure

The authors report no conflicts of interest in this work.