Researchers working with Professor Ron Chakraverty are trying to improve outcomes for patients who have allogeneic haematopoietic stem cell transplantation (allo-HSCT). This is where patients receive healthy stem cells from a donor, and it can be an important treatment option for many people who have blood cancer or a blood disorder. However, it is also a complex therapy and can have serious side-effects.
One such complication is Graft-versus-Host Disease (GvHD). This happens when T cells (a type of white blood cell) in the donated stem cells or bone marrow attack the patient’s own body cells. Doctors try to prevent this through the use of immunosuppressive drugs. However, this is not a perfect solution, as these drugs also slow down the recovery of the patient’s immune system.
The Chakraverty Group is addressing this challenging problem by looking at ways to optimise the recovery of the immune system following transplant - which is critical to protect patients from infections and prevent their cancer from returning. Their research focuses on T cells, which can be split into two main groups:
- CD8+ T cells - often called ‘killer’ T cells. These identify cancerous or infected cells in patients and directly eliminate them.
- CD4+ T cells - often called ‘helper’ T cells. These ‘orchestrate’ the immune responses, by helping other immune cells to make antibodies, by helping ‘killer’ CD8+ T cells to work better. However, they also take the longest of all major immune cell types to recover following transplant. In fact, CD4+ T cells can take up to 1-2 years to get back to normal healthy levels
To help answer this important question, the Chakraverty Group have conducted a clinical trial called PROT4. Patients were randomised to receive either an infusion of donor CD4+ T cells 100 days after the transplant, or no infusion.
Dr Andrew McIntyre (post-doctoral fellow) made an exciting discovery when analysing the blood samples given by patients in the trial. He found that CD4+ T cell infusion changed immune recovery dramatically, but in unexpected ways! He found evidence that the infused CD4+ T cells changed how well the CD8+ killer T cells recovered - both in number and how well they were working.
This discovery has led to new work - exploring how different types of CD4+ T cells can influence CD8+ T cells and if there are CD4+ T cell subsets that provide better ‘help’. Andrew hopes this will lead to the development of ‘designer’ CD4+ T cells that offer the best chance of improving immune recovery for people who may need a stem cell transplant in the future.
"The information we get from the clinical trials is incredibly important and can be used to design better approaches to improving immune recovery in the future. We thank all the patients and donors involved in contributing to this research." - Dr Andrew McIntyre.
Andrew is planning to publish the initial trial results to support further research in this field. Andrew also acknowledges the incredibly important role of patients and donors in this research. This includes the people who participated in the trial, as well as the patient and public advisors who inform the research processs.
The importance of this research to patients is explained by Mark Chatterley - who joined the BTRU in PCT as a Patient Partner and is also a member of the Project Management Group.
"Having a stem cell transplant can be a scary time for patients. It’s great to know that researchers like Dr McIntyre are looking into ways to improve the chances of a successful and complete recovery. It goes a long way to alleviate these fears." - Mark Chatterley, BTRU Patient Partner.