Stem cell transplantation is used to treat approximately 50,000 patients with blood cancers including leukaemia worldwide every year. For many patients, this potentially life-saving procedure is their only treatment option. Stem cell transplants given to patients contain a type of immune cell called a T-cell which come from the donor. The ability of donor T-cells to recognise and remove leukemic cells within the patient plays a major role in the curative action of stem cell transplantation.
Despite the widespread use of stem cell transplantation to treat blood cancers, there are major clinical challenges that need to be addressed. In some patients, donor T-cells don’t kill residual leukemic cells in the patient which can result in the cancer returning. In addition, in a proportion of patients, donor T-cells can attack normal tissues in the patient resulting in unpleasant side effects which can sometimes be fatal. There is an urgent need to understand how to make sure that donor T-cells efficiently kill cancer cells in the patient while at the same time preventing them from causing damage.
Now, Professor Linda Wooldridge from Bristol’s Faculty of Health and Life Sciences together with Dr James Griffin, Medical Director of Cellular Therapies at NHS Blood and Transplant (NHSBT), Professor Calliope Dendrou at the University of Oxford, Professor Mirjam Heemskerk and Dr Peter van Veelen at the Leiden University Medical Center, Professor Satu Mustjoki at the University of Helsinki, Dr Paul Brown at the University of Warwick and Dr Vanessa Venturi at UNSW Sydney, will work together to examine what enables donor T-cells to recognise and kill leukemic cells in the patient and why some donor T-cells start to attack normal patient tissues.
T-cells recognise and attack their targets via the recognition of ‘antigens’ which are expressed on the target cell surface. The researchers plan to use an antigen discovery approach to identify the antigens targeted by donor T-cells capable of killing leukemic cells and donor T-cells capable of attacking normal patient cells. An improved understanding of the antigens targeted by donor T-cells following stem cell transplantation will enable the future design of strategies to improve clinical outcomes for patients following administration of this therapy.
Professor Wooldridge, Chair in Translational Immunology and the study’s Principal Investigator, said: “For many patients, stem cell transplantation is their only treatment option and will successfully cure their blood cancer. However, there are some patients that are not cured by this treatment and may even suffer side effects that are severe or life-threatening.
“The Cancer Research UK funding provides an important opportunity for us to be able to further understand the immunological mechanisms behind the failure of stem cell transplants to cure patients and how they cause side effects. In the future, we hope that this research can be used to achieve improvements in clinical outcomes for this group of patients.”
Dr James Griffin, Medical Director of Cellular Therapies at NHS Blood and Transplant (NHSBT) and Honorary Senior Lecturer in the School of Cellular and Molecular Medicine at the University of Bristol, added: “Stem cell transplantation is one of the riskiest procedures routinely carried out in the NHS. The aim of promoting cure while avoiding side effects has remained elusive. Despite often being the only chance of cure, choosing to proceed to transplant can be a very difficult decision because of the impact of side effects on quality of life. This research offers hope in improving our understanding and improving the outcome for patients with blood cancer in the future.”