Scientists from UCL (University College London) have received £1.27million from Leukaemia & Lymphoma Research to improve bone marrow transplants, which often offer a last chance of a cure for patients with many different types of blood cancer.
Dr Clare Bennett and Dr Ronjon Chakraverty were granted the money to investigate the ways in which immune cells interact with each other to fight cancerous cells after the transplant.
When transplanted, donor bone marrow helps to replenish a healthy blood supply, repairing damage caused by chemotherapy. Among the blood cells transplanted are T-cells, white blood cells crucial to the body’s immune system that recognise alien cells and fight infection. In a process called graft-vs-leukaemia (GVL), these new T-cells hunt down any malignant leukaemia cells that have survived chemotherapy. Sometimes T-cells can become ‘worn out’ and stop working, reducing the GVL effect.
In many cases when the donor and patient are not an exact genetic match, donor T-cells also recognise healthy cells as ‘foreign’. The new immune system fights the patient’s body in a complication called graft-vs-host disease (GVHD). This can occur in up to half of all bone marrow transplants and can be life-threatening and cause long-term health problems.
The UCL team want to establish why sometimes donor immune cells do not work in the way it is hoped, either by becoming ‘worn out’ or by attacking the patient’s healthy cells. The researchers will focus on the function of dendritic cells, cells which identify foreign cells, process them and ‘present’ them to T-cells to attack.
Dendritic cells are especially prolific at activating immune cells directly after a transplant, enhancing the effects of GVL. However, they also produce signals that target the host’s cells, which leads to GVHD.
Dr Bennett said: “By studying how signals are transmitted between dendritic cells and T-cells to target foreign cells, we can develop ways to stop T-cells fighting the host and improve their cancer-targeting properties. This will make GVHD much less likely, as well as enhancing the T-cells’ abilities to fight leukaemia.”
Most GVHD takes place around the gut and the skin. By monitoring the dendritic cells’ behaviour around these areas the researchers hope to be able to understand how the T-cells are primed to attack the foreign cells. With this information, they can enhance the cancer-fighting signals that the dendritic cells emit, while blocking the messages that tell the new immune system to attack the host’s healthy cells.
Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said: “Bone marrow transplants often form a necessary part of blood cancer patients’ treatment. This research will target ways to make the GVL process even more effective as well as reducing the impact or severity of GVHD, which has a wider implication beyond blood cancer treatments.”