T Cells and their role in autoimmune diseases and leukaemia

The Challenge

T-cells are a population of white blood cells within our immune system that are critical to our defence against disease. T-cells process our dietary fuels (e.g., carbohydrates, protein and fat) to generate energy and building blocks required to generate and maintain a successful immune response. This process is called immune cell metabolism. Unfortunately, T-cells are dysfunctional in certain conditions such as various autoimmune disorders (e.g., rheumatoid arthritis and lupus*) and cancer (e.g., T-cell acute lymphoblastic leukaemia**). As a result of this dysfunction, T-cells derived from these patients have an altered metabolism. Excitingly, targeting this altered metabolic profile either in autoimmunity or leukaemia could lead to the development of new drugs and ultimately enter the clinic.  

^{*It is estimated globally that there are 5 million people living with the autoimmune disease Lupus and a further 18 million with rheumatoid arthritis. **In the UK there is an average of 791 cases each year of acute lymphoblastic leukaemia, mainly affecting very young children between 0 – 4 years old.}

The Method

Dr Nick Jones and his group are

• Investigating new drugs that target metabolic pathways in dysfunctional T-cells.
• Repurposing clinically available drugs, i.e. using them in another setting than they were originally intended for.

We are collaborating with global leaders in the fields of autoimmunity, immunology and leukaemia.

The Impact

• The team have discovered that repurposing a commonly used, type 2 diabetes drug called canagliflozin, stops T-cells (either derived from autoimmune patients or T-cell leukaemia cells) from functioning.
• The drug may be useful in treating autoimmune disorders, published in Cell Metabolism and supported by the Medical Research Council (MRC).
• Work is ongoing on the T-cell leukaemia side of the project supported by the Children’s Cancer and Leukaemia Group and Little Princess Trust.
• It is hoped that both projects can progress towards clinical trials.