University of Birmingham scientists have been awarded £1.6 million by Leukaemia & Lymphoma Research to improve the effectiveness of stem cell transplants for patients with blood cancers such as leukaemia and lymphoma.
Stem cell transplants can offer the chance of a cure for patients with cancer who have not responded to chemotherapy or radiotherapy. The transplant allows patients to receive higher doses of chemotherapy than would normally be tolerated and the donor bone marrow then replenishes a healthy blood and immune system for the patient. Unfortunately, the procedure is not effective in all patients and the cancer can return.
Interestingly a powerful ‘graft-versus-leukaemia’ effect develops after transplantation in which the donor immune system recognises remaining leukaemia cells as ‘foreign’ and kills them. This immune reaction is crucial to a transplant’s success. For the first time, the University of Birmingham researchers will examine these immune responses in the first few days after transplantation, leading to a better understanding of how they are generated.
In addition, the researchers have developed a way to vaccinate the healthy stem cell donor with proteins that can generate anti-leukaemia immune cells. If the donor’s immune system can be ‘primed’ to recognise cancer cells before transplantation, the graft-versus-leukaemia effect will be greatly improved. If preliminary trials are successful, the technique will become available to transplant patients in clinical trials.
As well as boosting the graft versus leukaemia effect, the project will focus on reducing side-effects of transplants by improving donor-patient genetic matching. Currently a stem cell donor is chosen that has similar immune-related genes to the patient, but it is not possible to achieve a perfect pairing. This means that the new donor immune system has genes that are slightly different from the patient’s. This enhances the graft-versus-leukaemia response but can also lead to side-effects if the new immune system attacks the patient’s tissue.
Professor Paul Moss of the University of Birmingham said: “This project will enable us to select better donor and recipient combinations, and to predict and intervene early in patients in whom we expect graft versus host disease to develop.”
Using a large amount of patient samples, the scientists will use cutting edge techniques to analyse for genetic similarities and differences between donors and patients.
Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said: “Stem cell transplants offer the last or often the only hope of a cure for many blood cancer patients and have improved greatly in recent years. The knowledge gained from this research could have a significant impact on survival rates when translated to the clinic.”