Professor Alan Melcher, Translational Immunotherapy Team
We are investigating systemic delivery of oncolytic viruses (OV) to tumours in mouse models, including in the brain. For example, we have shown that access of reovirus to tumours can be paradoxically enhanced by the presence of anti-viral neutralizing antibodies (NAb), which form complexes with reovirus for uptake, carriage and delivery to tumours by monocytes in the blood (Figure 1).
We are testing combination of systemic virotherapy (reovirus, herpes, coxsackie and maraba) with other immunomodulatory, clinical standard of care treatments (immune checkpoint blockade antibodies, targeted small molecules, radiotherapy and steroids). We use murine models and human in vitro immune assays (including use of patient samples) to complement our translational trial data (see below). This ensures we generate the most comprehensive pre-clinical dataset we can to optimize and guide future clinical development of novel OV and other immunotherapies.
We perform biological endpoint, translational trials to address biological questions in patients. We have shown, using window-of-opportunity studies in patients planned for surgical resections, that intravenous reovirus successfully accesses tumours in patients with cancer in the liver (Figure 2) or brain. We are now developing further such studies combining OV with other immunomodulators (currently granulocyte-macrophage colony-stimulating factor), to ensure continuous, iterative translational research between laboratory and clinic to inform future trial development and benefit to patients.