Bone marrow transplantation (BMT) can cure high risk leukaemia because the donor immune system is very effective at eradicating residual leukaemia cells. However, the donor-derived immune system can also cause tissue damage in the recipient, known as graft-versus-host disease (GVHD). Regulatory T cells (Tregs) can modulate the immune response and early phase clinical studies suggest that Tregs obtained from the bone marrow donor and infused into the recipient can help ameliorate GVHD. However, progress in the field is hampered by a lack of understanding of the fate of these Tregs after infusion because they cannot be distinguished from Tregs that are already pre-existing in the patients. Gene-marking involves the insertion of a unique DNA sequence that is integrated into the cell’s genome and passed on to all the cell’s progenies, thus enabling the infused cells and their progenies to be distinguished from endogenous non-gene-marked cells. In this world-first clinical study, we will use a form of gene-marking that enables the infused Tregs and all their progenies to be easily tracked by flow cytometry long term. This study will provide unprecedented insight into the fate of transferred Tregs in the clinical setting and whether their persistence, expansion and function can be improved with the co-administration of other drugs, such as interleukin-2. Because the infused Tregs can be readily distinguished from pre-existing Tregs, we will also be able to find out whether particular drugs have different effects on infused versus endogenous Tregs. This study is important because GVHD is a major cause of death after BMT. Furthermore, the use of Tregs is also being explored in other medical conditions including solid organ transplantation and type 1 diabetes.
Suitable for Honours and PhD students. Clinician researcher can also have a role in this project.