Douglas Mahoney, PhD

Cancers are heterogeneous diseases that, in many cases, are not effectively managed with existing treatments. Oncolytic viruses are promising biotherapeutic tools for cancer, whose clinical and commercial development is progressing rapidly. Currently, a major preclinical initiative in the field is to engineer next generation viruses or virus/drug combinations that break through the barriers to successful treatment. 

Our goal is to harness the innate cytokine response of the immune system — normally a major impediment to oncolytic virus therapy — to attack and kill tumours. Our preliminary experiments demonstrate one strategy to accomplish this: antagonizing the Inhibitor of APoptosis (IAP) gene family. In this case, a drug that antagonized the “Inhibitor of APoptosis” (IAP) gene family rewired tumour cells to initiate a self-destruct sequence upon exposure to cytokines, which were strongly induced in tumours infected with an oncolytic virus.  

To build upon these data, and to broaden the underlying concept, we propose a research plan to (1) elucidate the mechanisms responsible for synergy between oncolytic virus therapy and IAP antagonism, and (2) identify new opportunities to reprogram tumour cells to die in response to the cytokine cloud generated by oncolytic virus therapy.