Professor of Haematology & Cellular Immunotherapy
Graft-versus-host-disease, Graft-versus-leukaemia, T cell immunotherapy.
Our group is interested in understanding the biology of immune responses following allogeneic haematopoietic stem cell transplantation (allo-HSCT). Graft-versus-host disease (GVHD) is a major clinical problem and is caused by donor T cells within the graft that recognize antigens found in the patient but not the donor. Following allo-HSCT, activated donor T cells are recruited to peripheral organs where they cause severe injury, for example colitis or dermatitis. A similar immune reaction can occur in the lymphoid organs and bone marrow, a process co-opted therapeutically to achieve a graft-versus-leukaemia (GVL) effect. Although GVL can be separated from GVHD in experimental models, few of the identified strategies have been successfully translated into clinical practice. This failure reflects considerable redundancy in the mechanisms leading to GVHD and a lack of whole system approaches that readily address the complexity of this disorder.
Together with Dr Clare Bennett, we have developed clinically relevant pre-clinical models of allo-HSCT permitting us to track evolving immune responses in considerable detail and at multiple sites. We are working with computational biologists (Dr. Vincent Plagnol, Institute of Genetics) to develop a systems approach for identifying the cellular and molecular mechanisms that dictate the development of GVHD versus GVL. In particular, we are interested in how the mode of antigen presentation by different cells and tissues influences the type of immunity that is elicited. In collaboration with Prof. Hans Stauss, we are also using genetic engineering to modify the behaviour of anti-tumour T cells in vivo to subvert tolerance mechanisms that lead to relapse of cancers after initial control.
I am attending physician on the Bone Marrow Transplantation programme that runs at the Royal Free London and University College London Hospital, where I have a particular clinical interest in adoptive T cell therapy to prevent or treat relapse of leukaemia or lymphoma following allo-HSCT.
I am Chief Investigator of the national ProT4 Study that is testing the potential of transferring prophylactic allo-depleted donor lymphocytes following allo-HSCT.
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