Reovirus-induced immune modulation during oncotherapy

We don't normally think of viruses as beneficial organisms because they are invariably associated with human diseases. In 1998, we demonstrated that reovirus, a benign, naturally occurring human virus that does not cause any serious illness, is a potent cancer killer. This virus has the unique ability to preferentially kill cancer cells while leaving healthy, normal cells unaffected. Thus far, reovirus has been shown to kill cancers of almost every origin, including breast, pancreas, prostate, ovarian, brain, and colorectal. Reovirus is currently undergoing various cancer trials in Canada, the US, Belgium and the UK. Recently our laboratory discovered that reovirus-based anti-cancer therapy bears a "beneficial" side effect to it. We observed that, apart from its direct cancer killing activity, reovirus additionally educates the body's immune system to attack cancer. Importantly, this virus-induced anti-cancer immunity is capable of not only killing existing cancer cells, but also targeting any relapsing cancer cells in the future. Thus, reovirus-based therapy can simultaneously target cancers with two distinct mechanisms: 1) virus-mediated direct killing of cancer cells, and 2) virus-induced anti-tumor immunity. It is now acknowledged that anti-tumor immune activities are the indispensible components of reovirus therapy. For the last decade, we have comprehensively studied how reovirus directly kills cancer cells. We now focus on understanding the virus-induced immunological events in the context of cancers. For this purpose, we will first dissect the interaction between reovirus and the cancer-associated immune entities that dictate anti-cancer immunity. We will then use this knowledge to design strategies that can further enhance the efficacy of reovirus therapy. It is our hope that the knowledge generated through this project will result in better cancer outcomes, and further promote long-term cancer-free health even after discontinuation of therapy.