SEYMOUR GROUP

RESEARCH SUMMARY

Our research develops anti-cancer viruses that are able to infect and kill cancer cells, while leaving normal cells unharmed. This approach exploits the natural life cycle of the virus, which lyses infected cells in order to release progeny virus particles, allowing the infection to spread from cell to cell through the tumour. The life cycle of some viruses, such as adenoviruses, is intimately dependent on the activities of the cells they infect, and this provides a range of opportunities to engineer viruses that are only active when they encounter the specific environment of a tumour cell.

Adenoviruses can be designed that are dependent on deregulated cell cycle, dysfunctional apoptosis pathways, enhanced glycolytic metabolism and many others. In this way the virus amplifies itself within the tumour, reaching high local concentrations and potentially infecting all tumour cells. In addition this 'oncolytic' type of cell killing is very inflammatory, providing the possibility to create an anti-cancer immune response. These agents are often known as ‘oncolytic vaccines’.

Finally our viruses can be 'armed' to encode additional therapeutic agents, to be expressed only within the tumour; this provides a simple and versatile approach to targeted cancer therapy using a range of potent biological agents. For example encoding bispecific T cell engagers (BiTEs) can repurpose T cells within tumours to attack cells bearing any chosen antigen. Alternatively agents can be encoded to promote antigen-agnostic antigen cross presentation, important for systemic cancer vaccines, or to reverse the immune-suppressive functions of the tumour stroma.

IMPACT

The group has led to formation of various spinout companies and startups, including Psioxus Therapeutics, Macrophox, Theolytics, Native Antigen Company and Oxford Genetics. Each of these companies seeks to develop advanced technologies for improved human healthcare, and several company-sponsored clinical trials have been held in both the USA and Europe, alongside a handful of university-sponsored studies. In this way we seek to maximise the impact of our research, leveraging commercial funding sources for faster and more advanced development.