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Stem Cell Transplantation & Cellular Immunotherapy
Our group aims to translate state-of-the art cellular therapeutics from the laboratory to the clinic for the treatment either of opportunistic pathogens or of cancer, defining the limitations of such strategies within prospective clinical studies and further interrogating the mechanisms behind success or failure within murine models. Our mission is to improve anti-cancer cellular therapeutics by critically evaluating and manipulating both the host microenvironment and characteristics of the cellular product to enhance homing and to overcome local immune regulatory checkpoints, ultimately establishing novel therapies as standard treatment paradigms in the setting of both infectious disease and malignancy. Stem cell transplantation is probably the most successful example of the therapeutic potential of cellular immunotherapy, delivering cures in a significant number of patients with haematological malignancies. Whilst early approaches relied heavily on the cytoreductive activity of conditioning radio-chemotherapy, more recent developments have focused on optimising the ability of the newly established donor immune system to eradicate both residual host haematopoiesis and malignant cells that have survived the conditioning phase. Attempts to prevent uncontrolled alloreactivity and immune-mediated destruction of normal healthy tissues (graft-versus-host disease), which become increasingly relevant with greater genetic disparity between donor and recipient (e.g. unrelated donor or cord blood transplants), weaken cellular immunity and increase the risk of both infection and relapse. Our group is interested in immune reconstitution and adoptive cellular therapies for viral infections following stem cell transplantation. We are also interested in the development of immunological strategies to prevent or treat disease relapse following allogeneic transplantation. These approaches include modulation of the tumour microenvironment to enhance activity and genetic modulation of effector to cells to enhance function or re-direct specificity. We are currently leading 4 UKCRN national studies evaluating both cellular therapies for cytomegalovirus infection (CMV~IMPACT, CMV~ACE/ASPECT) and allogeneic immunotherapy in Hodgkin Lymphoma (PAIReD, ReACH).
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