Investigating the treatment of EBV-associated diseases with ex vivo expanded, genetically modified gamma delta T cells

Gamma delta T-cells (GDT cells) are a subset of white blood cells that act as part of the body’s defence mechanism against disease. These cells are thought to be involved in the immune response to infection by Epstein-Barr Virus (EBV) and the surveillance of EBV-positive tumour cells. The primary objective of this proposal is to investigate the use of modified GDT cells in the treatment of EBV-associated diseases. TC BioPharm are experts in the manufacture of GDT cells for cancer treatment and in this collaborative proposal, we aim to expand this therapy to the treatment of viral infections. GDT cells act by recognising a factor on the surface of virally-infected and cancer cells and from there initiate the death of these target cells. To enhance and direct this action, we propose to modify the GDT cells so that they will recognise EBV-specific proteins and therefore specifically target EBV infected cells. The project plan will be to design these EBV-specific recognition factors, generate the modified GDT cells and test their efficacy in cell culture and animal models. We hypothesize that these modified GDT cells will be superior in their ability to recognise and kill EBV-infected cells. The outcome of the proposed project will be directly applicable to EBV-infection and numerous EBV-associated cancers. More generally, the results of this project and the use of modified GDT cells, may be extrapolated to the treatment of other viral infections and virally-associated cancers (which account for ~15% of all cancers).