Advanced virotherapies for immuno-oncolytic applications

This project will develop refined virotherapies for the delivery immunotherapies in vivo.

Cross cutting methodologies spanning molecular, proteomic, structural and immunological studies will be employed better define how viruses infect cells, interact with host proteins and can be refined to mediate optimised delivery of immunotherapies to tumours.

Immunotherapy – the stimulation of the host immune system to fight cancer is having significant benefits across a range of cancer types. Amongst the most exciting developments are advances in “immune checkpoint inhibitors” (ICIs) which reactivate dormant T-cells to fight tumour cells, by interfering with negative regulators of T-cell activation. Systemic administration of these agents is associated with significant toxicity.

We have therefore focussed on a powerful means of delivering immunotherapies locally to the tumour, by encoding them within the DNA of tumour targeted viruses (“virotherapies”). This is extremely powerful since virotherapies hold unique potential to replicate and amplify millions of times over within the tumour microenvironment, though conditional, tumour selective replication, and can be engineered to overexpress additional therapeutic modalities, such as ICIs. No other therapeutic matches this selectivity or power, combining self-amplifying immune-stimulatory lytic effects with the added benefit of in situ production of therapeutic protein.To deliver ICIs within viruses, we have taken a two-pronged attack.

For further details of this project, please see our website: https://www.cardiff.ac.uk/study/postgraduate/research/programmes/project/advanced-virotherapies-for-immuno-oncolytic-applications