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UCL spin-out company BioVex was launched in 1999 to exploit research undertaken by David Latchman at the UCL Medical Molecular Biology Unit, Department of Biochemistry. (This department is now part of the Department of Structural and Molecular Biology, UCL/Birkbeck and Latchman is now Master of Birkbeck.) Biovex worked to develop inactivated herpes simplex viruses as therapies, and a promising dual-action oncolytic vaccine for solid tumours, OncoVEXGM-CSF, was taken into successful Phase II trials. In 2011 the company was bought out by Amgen for $1 billion — still the largest ever cash sale of a UK biotech — and Amgen has now taken this virus into a Phase III trial with promising initial results.
Viral infections pose a significant risk of long-term disease and death to cats. In Europe alone, over 30 million domestic cats are vaccinated each year against three core pathogenic viruses. Research performed at the University of Glasgow has systematically supported the development of key technologies against major feline viral diseases. This work has delivered incremental but wide-reaching benefits to veterinary healthcare and animal welfare by providing: (i) reagents used in the diagnostic industry; (ii) viral screening services for big cat conservation programmes; (iii) developmental input into the creation of one of the most efficacious and widely used vaccines against feline leukaemia virus; (iv) testing of feline vaccines for efficacy and safety; and (v) development of best practice guidelines and training for veterinary practitioners on feline viruses.
Research at the University of Oxford into molecular evolution led to the development of BEAST, a powerful suite of computer programs for evolutionary analysis. Viral genome sequences from infected populations can be analysed to infer both viral population history and epidemiological parameters. This approach has been used to track and predict the transmission and evolution of pathogens, particularly viral infections of humans such as influenza and HIV. BEAST was used alongside traditional epidemiological methods by the World Health Organization to rapidly assess and identify the origins of the 2009 H1N1 `Swine Flu' pandemic; immediate recommendations for necessary international action followed. This approach is now widely adopted by health protection agencies and health ministries around the world and is being applied to understand viral diseases of both humans and animals.
Recent outbreaks across Europe of Bluetongue, a viral disease particularly affecting sheep, have driven research at LSHTM by Professor Polly Roy and her team, resulting in the Bluetongue virus (BTV) becoming one of the best understood viruses at the structural and molecular levels. The research has ultimately enabled the creation of several promising new vaccines. In addition the Roy group has contributed towards exploiting virus-like particles (VLPs) as a method to produce safe vaccines against human and animal viral pathogen. The most advanced example is a BTV vaccine for livestock, which is manufactured by Boehringer Ingelheim (BI).
Highly Active Anti-Retroviral Therapy (HAART) is a combination of drugs used to effectively control HIV infection. Since 1987 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) had been used in HAART combinations to specifically target HIV-1 reverse transcriptase, however, resistance and side effects soon prompted the need for an alternative. In 1998, University of Oxford Professors David Stuart and David Stammers provided the first detailed structural framework to facilitate the design of a highly effective alternative class of drug, the Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). NNRTIs have since been developed for clinical use, impacting the pharmaceutical industry and profoundly improving the quality of life of patients.
Oxford Expression Technologies (OET) is a spin out company launched jointly by Oxford Brookes University (Brookes) and the Natural Environment Research Council (NERC) to exploit Intellectual Property (IP) in the field of protein expression using novel insect virus vectors. OET generates revenue through sale of kits, services & licences to a range of global customers including academia, research institutes, pharmaceutical and biotechnology companies. OET provides employment, invests in in-house Research and Development including funding collaborative PhD students, and generates royalty income streams for Brookes and NERC. Customers are able to produce multiple recombinant proteins to higher yields and quality than was otherwise possible and a number of companies are using the developments for the commercial production of vaccines and other uses.
Researchers from the University of Oxford identified the novel human protein Forkhead box transcription factor 1 (FOXP1) and showed it to be an important prognostic biomarker in cancer. Expression of FOXP1 can distinguish those patients with diffuse large B-cell lymphoma (DLBCL) who are at high risk of disease progression, making it possible for clinicians to target more intensive therapy to this group. DLBCL accounts for one third of lymphomas and is the seventh commonest form of cancer. The anti-FOXP1 monoclonal antibody developed by Oxford University is now used worldwide in clinical diagnostics.
Research involving mathematical modelling is helping to unravel the complexities of key areas of biomedicine. Our study of the mammalian immune system focuses on two areas: (1) genetic evolution of HIV within the host during infection, and (2) dendritic-cell-based immunotherapy. The research has influenced understanding by biomedical practitioners of control parameters, the immune response and viral resistance to drugs. The involvement of mathematicians has led to a paradigm shift which has provided clear directions for investigation, and insights into immunisation programmes (an area of research which is still an emerging field).
Research from the University of Oxford has played a major role in the development of effective vaccines to combat the urgent worldwide problem of influenza. This methodology, licensed to AstraZeneca, has been used to prepare the currently licensed live attenuated influenza vaccine FluMist. Since its introduction in 2006 it is estimated that FluMist or other vaccines produced using reverse genetics have saved the lives of thousands of people worldwide who would otherwise have died from flu and its complications. FluMist has generated close to $1 billion income for the manufacturers (MedImmune, owned by AstraZeneca).
Research at the UCL Institute of Child Health (ICH) has led to the successful treatment of children with primary immunodeficiency diseases for whom there was little chance of "cure" by the only other possible means: haematopoietic stem cell transplantation (HSCT). Beginning in 2002, we have treated 32 patients with four different primary immunodeficiency disorders. In total we have treated 12 patients with severe combined immunodeficiency (SCID-X1), 13 patients with adenosine deaminase deficient severe combined immunodeficiency (ADA-SCID), 5 patients with chronic granulomatous disease (CGD) and 2 patients with Wiskott-Aldrich syndrome (WAS). Most of the patients have been successfully treated and are at home, off all therapy. We are now starting to develop this technology to treat a wider range of related disorders.