Translational Immunotherapy Research Group
Group Leader: Dr Mark Lowdell
The Group’s interests centre on the study of the immunology of bone marrow transplantation incorporating immunotherapy, immune reconstitution and graft-versus-host disease (GvHD) with a special focus on translational research. Currently the group is responsible for 4 phase I or II clinical trials including a completely novel natural killer cell therapy which is being trialled in patients with AML.
The group identified a previously unknown tumour-restricted pathway for NK cell activation and translated this into a clinically-relevant procedure which was finally approved by the MHRA for phase I trial. NK cells activated in this manner do not target allogeneic normal cells/tissues but are highly cytotoxic to many haematological cancers and some solid tumours including breast and ovarian cancer cells. Additionally the group is running a phase I/II trial of CMV-reactive allogeneic T cells to prevent/treat CMV reactivation post haematopoietic stem cell transplant. Preliminary data have been published and have led to a Wellcome Trust funded phase III multicentre trial in conjunction with a UK biopharma company.
The group controls a dedicated “clean room” facility for the production of cell therapies as “investigational medicinal products” for clinical trials under licences from the Human Tissue Authority and the Medicines & Healthcare Products Regulatory Agency.
The group has now realised the UCL-Royal Free BioBank at the Royal Free campus.
Björkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R, Lahiri N, Raibon E, Lee RV, Benn CL, Soulet D, Magnusson A, Woodman B, Landles C, Pouladi MA, Hayden MR, Khalili-Shirazi A, Lowdell MW, Brundin P, Bates GP, Leavitt BR, Möller T and Tabrizi SJ (2008). A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington’s disease. J ExpMed;205:1869-77. Pubmed
Mattes FM, Vargas A, Hainsworth EG, Sweny P, Nebbia G, Lowdell M, Klenerman P, Phillips RE, Griffiths PD, Emery VC. (2008) Functional impairment of cytomegalovirus specific CD8 T-cells predicts high level replication after renal transplantation. Am J Transplantation;8:990-9. Pubmed
Mackinnon S, Thomson K, Verfuerth S, Peggs K, Lowdell MW. (2008) Adoptive Cellular Therapy for Cytomegalovirus Infection following Allogeneic Stem Cell Transplantation using Virus-Specific T-cells.
Blood Cells Mol Dis.;40:63-7. Pubmed
North J, Bakhsh I, Marden C, Pittman H, Addison E, Navarrete C, Anderson R, Lowdell MW. (2007) Tumor-primed human natural killer cells lyse NK-resistant tumor targets: evidence for a two-stage process in resting NK cell activation. Journal of Immunology; 178:85-94. Pubmed