INVESTIGATING THE POTENTIAL OF T CELLS ISOLATED FROM JUVENILE THYMUSES FOR THE DEVELOPMENT OF ALLOGENEIC THERAPIES FOR AUTOIMMUNE CONDITIONS (SELECT)

Anais Makos, Lesley Smyth^†, Aled Clayton^#, Rafael R Guerrero*, Dan Hawcutt*, Oksana Kehoe

^†University of East London, ^#Cardiff University ; ^*Alder Hey Children’s Hospital, Liverpool

Funded by the Orthopaedic Institute

One in every 16 of people in the UK live with an autoimmune condition causing them pain, difficulty, lost opportunities in work and in life and in many cases placing them at risk of early death. Autoimmunity occurs when the immune system attacks the body. Regulatory cells (also called Tregs) are cells of immune system which have a role in regulating or suppressing other cells in the immune system. Tregs control the immune response to self and foreign particles and help prevent autoimmune disease. Understanding how Tregs supress cells in the immune system could help improve treatments for people with autoimmune conditions including lupus, type 1 diabetes, Sjögren syndrome, multiple sclerosis and rheumatoid arthritis.

Scientists at the RJAH have a long history of developing novel cell-based therapies for arthritis. To further our studies, we wish to collect discarded human thymuses, routinely removed during paediatric cardiac surgery at Alder Hey Children’s NHS Foundation Trust. We intend to study the potential of immune cells derived from thymuses in the treatment of other patients with inflammatory arthritis. Many types of cells and molecules can be derived from tissues removed from patients undergoing cardiac surgery. Some of these tissues have received considerable interest as potential cell sources for cell-based therapies for autoimmune conditions.

The safety of immunotherapy of cells from thymuses (Tregs) have been demonstrated in patients with systemic lupus erythematosus and type 1 diabetes. Results from the first clinical trials demonstrated successful isolation and purification of Tregs, expansion in GMP facilities and re-infusion in patients with improvement in clinical outcomes. Next, this project will explore how the Tregs function. We will add the cells into a dish with immune cells from patients with rheumatoid arthritis. These cells are overactive, which causes the pain, inflammation and swelling in the joints, so we want to see if our Tregs from paediatric thymuses can suppress these immune cells. If these experiments are successful and Tregs contain anti-inflammatory properties, then they have the potential to be applied to many different autoimmune conditions.

This is very exciting project in collaboration with clinicians from Alder Hey Children’s Hospital in Liverpool. We are dealing with the ethical approval and recruitment of a Research Assistant. We hope to start this project in late autumn 2023.