Grant: Operating Grant

Despite our best efforts, the current success of brain cancer therapy is essentially the same as it was 35 years ago. The biological difficulties inherent to brain cancer - such as the diffuse and multifocal nature of heterogeneous tumours in a minimally regenerative organ - have proven difficult to address. Clearly, innovative new approaches are necessary to successfully improve patient outcomes. Over that past decade, we have been pursuing the use of replicating "oncolytic" viruses that preferentially infect and kill tumour cells, choke off tumour blood supplies, and draw in anti-tumour immune responses, that can lead to cures in very challenging tumour models and early human trials. However, oncolytic virus therapy of brain cancers has lagged behind. This is largely because the best oncolytic viruses developed thus far are either not safe enough to be administered in the brain (Vaccinia virus, Vesiculoviruses) or are so attenuated that they show little efficacy against aggressive brain cancers (Herpes). We have developed an entirely new, very potent but safe oncolytic virus platform for the treatment of brain cancer: Farmington virus. The work proposed in this application is directed at removing the last remaining bottlenecks to defining a clinical candidate virus for human trials. Firstly, we seek to increase the breadth of brain tumours that farmington viru can treat by adding additional tumour killing mechanisms and improving spread of the virus in tumour beds and to disseminated metastases. In addition, we seek to further harness the patient's immune system to attack their own tumour by engineering brain tumour antigens into the oncolytic virus to act as a vaccine. We propose this "one-two punch" strategy will combine the best of two exciting therapeutic fields of study": oncolytic viruses and immunotherapy, and will focus them against a critically unmet medical need.