Development of an effective therapeutic regime for preventing cancer recurrence after surgery using a novel viro-immunotherapeutic agent

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Despite advances in surgical techniques, survival rates for oral sqamous cell carcinoma, the most common form of oral cancer (398,000 patients worldwide in 2012), have not improved for the last 20 years. 50-70% of patients die within 5 years due to local recurrence and remote metastasis. The prognosis of patients with recurrent or metastatic head and neck squamous cell cancer is generally poor. The median survival in most series is six to nine months depending upon patient- and disease-related factors. Therefore, new approaches are urgently needed to prevent recurrence and metastasis after surgery. The main source for recurrence and metastasis after surgery is minimal residual disease (MRD) that remains in situ after surgical resection in microscopic deposits beyond the clearance margins and in micrometastases. There is increasing evidence that surgical intervention can actually promote tumour recurrence and distant metastases by several mechanisms including suppression of host immune cells, such as natural killer (NK) cells and T cells. Tumour-targeted oncolytic viruses (TOVs) are attractive therapeutics for cancer because they selectively amplify through replication and spread the input dose of virus in the target tumour and most importantly kill tumours by multiple mechanisms, in particular they can induce systemic anti-tumour immunity that can target MRD. We have recently created a novel tumour-targeted oncolytic vaccinia virus. Treatment with this virus resulted in a strong NK cell activation and potent tumour-specific immunity, and dramatically reduced lung metastasis after surgery in several cancer models when the virus was intratumurally injected before surgery. To improve its anti-tumour efficacy further, we now have engineered the mutant virus with a particular therapeutic gene that can boost the activity of NK cells and anti-tumour T cells further. In this project, we will evaluate the feasibility, efficacy and safety of this novel immunotherapeutic agent for preventing recurrence and metastasis of cancer after surgery in a serious of tumour models that can mimic the clinical situation of cancer patients. By the end of this project, an optimal therapeutic regime will be developed. These data will provide proof of concept for translation of the regime into clinical trials. This new approach may significantly improve the survival of head and neck cancer patients in the future.