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.
Together the University of Aberdeen and Aberdeen city have become a major centre for biologics, the synthesis of medicines from compounds derived from living organisms. Commerce and industry have invested heavily in the process, creating specialist knowledge, jobs and an internationally-recognised network of expertise that promises further growth. This has arisen from ground-breaking research in Aberdeen into the VNAR antibody class that are the smallest binding sites so far identified in the animal kingdom and led to the validation of a new drug discovery platform. Spin-out companies were created (Haptogen Ltd, Cyclogenix Ltd and the pre-commercialisation vehicle Elasmogen) to exploit the emerging technology, which has completed successful efficacy trials in several animal models including late stage pre-clinical models, with trials in humans expected.
The claimed impact is therefore that: spin-outs have been created, highly skilled people have taken up specialist roles in companies; industry and venture money has been invested in patent protected research and development, business has adopted a new technology, award winning industry collaborations have been forged and jobs have been created.
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.
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.
Proteins are fundamental to life and to many drugs, vaccines and new types of applied medicine with engineered cells. For this work, it is often essential to tag proteins to enable their identification and purification. The V5 tag, which was developed in St Andrews, is used very widely in this role and has some key advantages over alternatives.
Key impacts are:
In the initial stages of the drug-discovery process, a range of synthetic molecules are developed and the most promising ones are selected for further development into potential drugs. The research of the Surrey team in collaboration with a research team at Pfizer sheds new light on how to achieve high efficacy, by using mathematical modelling to speed up this selection process. The research has led the pharmaceutical company Pfizer to terminate a discovery project and redeploy resources in a new direction. This research has generated direct impact in the field of early-stage pharmaceutical research, and indirect impact on the economy and health.
Southampton research underpins the clinical development of a new class of anti-cancer monoclonal antibodies (mAb), such as anti-CD40, anti-CD27 and anti-CD20. The most advanced is a next generation, fully human drug, ofatumumab (commercialised by GlaxoSmithKline/Genmab; trade-name Arzerra) approved in Oct 2009 to treat advanced chronic lymphocytic leukaemia. Its approval was based on a 42% response rate in patients who had failed current `best in class' treatment. Arzerra is now a multi-million dollar drug, launched in 26 countries (and growing) and is being used in 19 on-going clinical trials worldwide for diseases ranging from lymphoma to rheumatoid arthritis and multiple sclerosis. Southampton's work has inspired follow-on funding from government and industry in excess of £12m.
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.
The CATH classification of protein structure, developed at the Institute of Structural and Molecular Biology, UCL, by Janet Thornton and Christine Orengo, has been used widely across the pharmaceutical industry and academia to guide experiments on proteins. This has led to significant cost and time savings in drug discovery. The UCL-hosted online CATH database receives around 10,000 unique visitors per month, and is a partner in InterPro — the most frequently accessed protein function annotation server available.
Annually in the UK ~110,000 donor platelet concentrates are used to prevent bleeding in cancer patients and ~660 newborns are born with an increased risk of bleeding because of a low platelet count caused by maternal platelet antibodies. These newborns and ~10% of the cancer patients require donor platelet transfusions matched for the platelet antibody because non-matched donor platelets are clinically less effective. University researchers have developed better methods for platelet antibody detection and typing and as a direct consequence of this research NHS Blood and Transplant (NHSBT) has from 2009 onwards been able to make platelet transfusions safer and clinically more effective, thereby reducing the number of severe, and on occasions life- threatening, bleeding episodes.