Temporospatial onco-viro-Immunome analysis for deciphering, therapeutic targeting and strategic management of the immunological determinants of virus-assisted anti-cancer immunotherapy

A cancer-killing virus known as reovirus is currently being tested in humans for the treatment of various cancers. Recently it was found that, in addition to its cancer-killing properties, reovirus educates our immune system to identify and attack cancer on its own. Hence, through cutting-edge technological advances and international collaborations, this project aims to develop therapy options that will simultaneously promote the cancer killing activities of both reovirus and the immune system. These revolutionary cancer therapy options promise to not only kill existing cancer cells, but also establish a long-term protection against cancer relapse even after the discontinuation of therapy. Dr Patrick Lee?s research team is internationally known for the discovery of reovirus. Reovirus is currently being tested in humans for the treatment of various cancers. Recently his team found that, in addition to its cancer-killing effect, reovirus educates our immune system to identify and attack cancer on its own. Thus, if properly harnessed, a virus-driven immune response can complement and greatly enhance the efficacy of reovirus therapy. The quality of immune response is dictated by the epitopes- 8-11 amino acid long peptides found in the grooves of specialized MHC molecules present on all nucleated cells. Thus, comprehensive information on the peptides from MHC molecules (together known as MHC peptidome) is imperative in devising interventions to promote beneficial anti-cancer immune responses. Currently, the MHC peptidome that accompanies reovirus therapy is completely unknown- mostly due to the enormous magnitude of peptides bound to MHC molecules. However, current technological advances in the field of proteomics, bioinformatics and immunology now make it possible to take upon this challenge. To achieve this, the researchers have joined forces with the leading expertise in proteomics at the Harvard and UK, and aims to: 1) discover the epitopes that shape the immune responses accompanying reovirus therapy, and then 2) to exploit this knowledge to devise highly efficacious anti-cancer therapy. The team?s ?organic? approach aims to learn from nature. It focuses on understanding the immunological determinants that dictate the outcome of a battle between a naturally occurring cancer-killing virus and cancer, and plans to exploit this knowledge to devise a highly efficacious cancer immunotherapy. The researchers believe that the information derived from this project will pave the way for anti-cancer vaccines as well as anti-cancer therapies. Most importantly, the knowledge synthesized here can be readily translated for use in humans under clinical settings. Thus, the findings from this project bear a potential to revolutionize the way cancers are managed and reduce the rates of cancer incidence and related mortality in Canadians.