Log in
Kidney disease affects about 10% of the population and 10% of these patients develop established kidney failure (ERF). Transplantation is a better treatment for ERF than dialysis but is limited by acute and chronic graft rejection. Treatment of rejection mediated by the recipient's T-lymphocytes is now remarkably successful, but antibody-mediated rejection (AMR) remains challenging. A principal cause of AMR is recipient antibodies targeting human leukocyte antigen (HLA, also known a tissue type) on the transplant organ. The presence of such antibodies previously vetoed transplantation but in the last ten years it has become increasingly feasible to transplant across HLA antibody barriers. Research at the University of Warwick (UoW) by Dr Daniel Zehnder and Professor Robert Higgins has facilitated and accelerated this process. Their research includes the first detailed monitoring of antibody levels after transplantation, showing how these affect graft function, and the development of new techniques to remove antibodies from patients. This resulted in over 100 HLA-mismatched renal transplants taking place in Coventry giving a net saving to the NHS of over £5M. Their research and its clinical translation encouraged the performing of another 350 such transplants across the UK and initiation of the National Case Registry.
Research conducted by Professor Jo Bradwell at the University of Birmingham provided the basis of the commercially available diagnostic test Freelite®, which quantifies free immunoglobulin light chains in serum and was the first and only assay for the diagnosis and monitoring of Multiple Myeloma (MM). MM is a cancer of immunoglobulin producing plasma cells in the bone marrow. Freelite® has markedly improved the diagnosis and management of MM, is helpful in the diagnosis of all B cell lymphoid neoplasias and provides prognostic information for premalignant conditions present in over 3% of people over 50 years of age. Freelite was commercialised by the University of Birmingham spinout company, the Binding Site, which has achieved worldwide sales, with over 360,000 tests being sold per month in 90 countries and an ongoing 25% annual growth in sales. The company provides annual revenue of £55m and employment for 620 people in the UK and abroad. An improved second generation of tests has been developed by Professor Mark Drayson at the University of Birmingham, which has been commercialised by a second University spinout company Serascience, which started marketing a point of care free light chain diagnostic test worldwide in April 2013.
BioAnaLab's mission is to advance innovative biopharmaceuticals, such as therapeutic antibodies for cancer treatment, into the clinic. From 1995, the University of Oxford pioneered methodology essential for validating top quality therapeutic antibodies and monitoring their activity in patients. This expertise led to the establishment in 2002 of BioAnaLab, a successful Isis Innovation spin-out company. By 2009 BioAnaLab employed 50 staff providing analytical services to approximately 100 pharmaceutical and biotechnology companies worldwide and had annual sales exceeding £3.13 million. BioAnaLab was subsequently acquired in 2009 by Millipore Corporation to become an integral part of Merck/Millipore's global drug discovery unit.
Research into modified Fc regions for therapeutic antibodies has resulted in the development of antibodies with novel and optimised functions. An aglycosylated anti-CD3 antibody called otelixizumab has reached phase 3 clinical trials with GSK and a novel antibody for treatment of fetomaternal alloimmune thrombocytopenia has been tested in human volunteers. The patented technology has been licensed to Pfizer and to GSK for incorporation into their therapeutic antibody programmes with four of these already in clinical trials (tanezumab, ponezumab, RN316 & RN564). Licensing revenue totalling £3.2 million has been returned to the University's company Cambridge Enterprise Ltd in the impact period. In addition, consultancy and advisory services on antibody engineering have been provided to a number of other biopharma companies.
The production and use of monoclonal antibody, ALK1, by researchers in Oxford has been pivotal in enabling the accurate diagnosis and treatment of Anaplastic Large Cell Lymphoma (ALCL). This research also led to the formal classification of ALK-positive ALCL tumours by the World Health Organization in 2008. While ALCL accounts for 10-20% of paediatric/adolescent non-Hodgkin's lymphoma worldwide, its diagnosis had been problematical due to the absence of suitable reagents. This was remedied in 1997 when Oxford researchers created the first monoclonal antibody, ALK1, recognising anaplastic lymphoma kinase (ALK), a molecule that is associated with up to 90% of ALCL.
Research conducted by a multidisciplinary team of oncologists and scientists at the University of Southampton has driven major advances in lymphoma care, leading to the development and standardisation of effective new antibody treatments and optimal drug regimens. Through their direction of international clinical trials, they have influenced care for Hodgkin and Burkitt lymphoma in the UK and internationally, affecting all stages of patient-experience from diagnosis to treatment. Their findings underpin significant improvements in survival and quality of life for the 14,000 people affected by lymphoma in the UK each year.
Invasive pulmonary aspergillosis (IPA) is a frequently fatal disease of haematological malignancy patients, caused by fungi from the genus Aspergillus. Dr Christopher Thornton has developed and commercialised a novel point-of-care test for the diagnosis of IPA with an Aspergillus-specific monoclonal antibody (mAb) JF5 generated using hybridoma technology. Using this mAb, he has developed a lateral-flow device (LFD) for the rapid detection of Aspergillus antigen in human serum and bronchoalveolar lavage fluids (BALf) that signifies active infection. Commercial exploitation of the patented technology has been met through the establishment of a University of Exeter spin-out company, Isca Diagnostics Limited.
The discovery of an early Acute Traumatic Coagulopathy (ATC, a syndrome of abnormal clotting after trauma) by Professor Brohi's team in 2000, and subsequent work building on that pivotal discovery, has led to [A] a new understanding of why patients bleed to death after severe injury and resulted in [B] a fundamental change in resuscitation strategy for acute bleeding patients (`Damage Control Resuscitation') that has led to [C] a 250-300 per cent improved survival in massively bleeding trauma patients. Discovering the character and mechanism of ATC has led to [D] new research in diagnostics and therapeutic opportunities to further improve outcomes. These rapid changes have led to [E] new forums for professional education and [F] improved public understanding of science and medicine.
Impact: Health and wellbeing; translation of a clear evidence base for reducing red blood cell use in intensive care and surgery into guidelines and changed clinical practice.
Significance: A 20% reduction in overall UK red blood cell usage between 2002-2012, saving the NHS approximately £100M annually; 7000 fewer patients are exposed to red cell transfusion annually, saving 500 lives.
Beneficiaries: Patients in intensive care units; the NHS and healthcare delivery agencies.
Attribution: Studies were led by Walsh at UoE with NHS and Canadian collaborators.
Reach: 7000 patients per year, UK-wide; incorporation into international guidelines.
King's College London (KCL) research has made a major contribution to improving the quality of life for patients who have anaemia linked with chronic kidney disease. Studies undertaken by KCL researchers established that intravenous iron supplementation was required in anaemic patients with advanced kidney disease, in whom oral iron therapy was ineffective, and defined the best regimes for administration of intravenous iron. Subsequent KCL work on drugs that stimulate production of red blood cells (erythropoiesis) defined the target levels of haemoglobin to aim for in chronic kidney disease patients. Most recently, KCL researchers made the key discovery that the novel drug peginesatide for the first time enables the rescue of patients who develop a rare and potentially fatal reaction against erythropoietin (which is the commonest treatment for anaemia in chronic kidney disease). These KCL research studies have had a significant impact by making a major contribution to national and international clinical guidelines, including UK NICE guidelines and the 2012 National Kidney Foundation KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease.