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Clinicians and scientists at UCL have been central to the design and management of single centre and multi-centre lymphoma trials within the UK and internationally. The trials have enabled a balanced approach to the non-Hodgkin lymphomas (NHL), supporting more conservative strategies in certain well-defined situations but also providing evidence for the value of very intensive therapy in appropriate patients. These trials have contributed to patient survival, quality of life and appropriate resource utilisation.
Alemtuzumab, a humanised therapeutic antibody, is a major addition to the repertoire of immunosuppressive agents used for organ and stem cell transplants. Administered as an induction agent in a short course of treatment, alemtuzumab reduces the incidence of graft rejection without preventing recovery of the patient's ability to fight infection. Alemtuzumab also decreases graft versus host disease, a vital factor in the treatment of aplastic anaemia and acute leukaemias. Furthermore, its important role in minimising immunosuppressive therapy helps prevent treatment-associated problems for the patient. Currently used off-licence for transplants, alemtuzumab improves patient survival and healthcare.
Research conducted at UCL/UCLH over the last 20 years has enabled the identification of adults with acute leukaemia who are most likely to benefit from the use of stem cell transplantation, i.e. those with acute leukaemia in first remission. The treatment is highly intensive, potentially toxic and expensive high-dose chemotherapy followed by haemopoietic stem cell transplantation, and is inappropriate for some patients. The work has made a major contribution to the development of guidelines worldwide for the treatment of this disease. Improved patient selection for transplantation results in improved survival, less toxicity with improved overall quality of life, and a more appropriate use of NHS resources.
Seven patients with avascular necrosis of the femoral head and bone cysts have been treated successfully with skeletal stem cell therapy, developed by Southampton researchers, resulting in an improved quality of life. This unique multi-disciplinary approach linking nano-bioengineering and stem cell research could revolutionise treatment for the 4,000 patients requiring surgery each year in the UK and reduce a huge financial burden on the NHS. The work has been granted three patents and the team are in discussions on development of the next generation of orthopaedic implants with industry.
We were the first to show that human stem cells could be used to create functional organ replacements in patients. These transplants, first performed to save the life of an adult in 2008, and then repeated to save a child in 2010, have changed the way the world views stem cell therapies. We have opened the door to a future where conventional transplantation, with all its technical, toxicity and ethical problems, can be replaced and increased in range by a family of customised organ replacements, populated by cells derived from autologous stem cells. This has altered worldview, changed clinical practice and had key influences on UK policy.
T lymphocytes recognise antigens in the form of an HLA-peptide complex. HLA-peptide tetramers consist of a fluorescent HLA protein and peptide which together bind to, and therefore identify, T cells that recognise this HLA-peptide complex. As such they have proven to be a revolutionary reagent in immunology. Professor Paul Moss at the University of Birmingham has played an integral role in the clinical and commercial application of tetramers, particularly around the cytomegalovirus (CMV)-specific immune response in the context of monitoring immune recovery after transplantation and pioneering a new approach for cellular immunotherapy. The impact of this research relates to the clinical management of CMV infection in immunosuppressed patients and the creation of Cell Medica, a UK Biotech company pioneering tetramer-based cell therapy, thus demonstrating impact on clinical practice and the UK economy.
Research led by University of Oxford scientists has resulted in widespread use of the humanised therapeutic antibody, Campath (alemtuzumab), in patients with chronic lymphocytic leukaemia (CLL). Licensed by both the European and American regulatory authorities in 2004 for the treatment of CLL, Campath is used as first-line treatment for patients with aggressive forms of the disease and following relapse. It can induce long-term clinical remission even in cases resistant to other drugs. Campath has now been used in approximately 15,000 patients, and has generated revenues of approximately £750 million from the licensed treatment of CLL.
Chronic myeloid leukaemia (CML) is a rare blood cancer, with around 560 new cases diagnosed in the UK each year. Research conducted by Professor Tessa Holyoake's team at the University of Glasgow has led drug development and stimulated clinical trials of therapies targeting CML stem cells at two major pharmaceutical companies (Novartis and Bristol-Myers Squibb). The researchers are listed as co-inventors of a novel compound (LDE225) and have promoted two further therapies targeting CML stem cells (BMS-833923 and hydroxychloroquine) into clinical trials as treatments for CML. Holyoake also had a key role in establishing the Paul O'Gorman Leukaemia Research Centre in May 2008, funded by more than 1,800 charitable donations totalling around £2.6 million and giving patients unprecedented access to the latest clinical trials.
Research at UCL pioneered B cell depletion to treat rheumatoid arthritis (RA) and also stimulated the development of B-cell-directed therapies for other autoimmune rheumatic, haematological and neurological diseases. Now NICE approved, B cell depletion (based on rituximab) in RA is as effective as the alternative (anti-TNFα drugs) and an option for patients unable to gain benefit from anti-TNFα drugs. Rituximab offers drug-cost savings of up to £5,000/annum/patient and for many is a more convenient therapy, being given as an infusion only every five months apart, or more. B cell depletion has also proved to have an excellent safety profile, with many receiving repeated courses of treatment. As a consequence of UCL research, rituximab has brought substantial benefit to patients with many autoimmune diseases, including over 200,000 who have been treated with rituximab for RA so far.
Neural stem cells offer enormous therapeutic potential for stroke but they require regulatory approval. Researchers at King's College London (KCL) devised a technology to immortalise stem cells, generated clinical-grade neural stem cell lines and demonstrated efficacy in an animal model of stroke. KCL research underpins the first approvals in the UK for a therapeutic stem cell product. This led to an industry-sponsored clinical trial of a stem cell therapeutic that has demonstrated vital improvement in all the first five stroke patients treated. KCL research has made a significant impact by considerably reducing the timetable for delivering potential therapies which will affect the life sciences industry and the process now in place acts as a model for other technology developments in this area.