An increased understanding of the role of the body's immune system in the development of diseases such as prostate cancer, squamous cell carcinoma (a type of skin cancer), type 1 diabetes, autoimmune liver disease, and in the rejection of transplanted organs by some transplant patients, has paved the way for a pioneering research programme which aims to develop 'enhanced' cells as therapies. Researchers hope to find ways to extract specific cells which play a role in these diseases from patients, then activate or modify them in the laboratory and transfer them safely back into patients so that they can fight the diseases from within their own body.
The £1 million research programme is being carried out at the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) at Guy's and St Thomas' and King's College London, working in partnership with King's College Hospital. Researchers expect to conduct the first clinical trials in patients within the next few years, manufacturing these 'enhanced' cells in new licensed premises at Guy's Hospital.
Their work will focus on the cells which cause unwanted immune responses in the development of conditions such as type 1 diabetes, autoimmune liver disease and transplant rejection, as well as the cells that do not respond adequately in preventing certain cancers from developing.
Professor Mark Peakman, Infection and Immunity theme lead within the BRC, said: "One of the problems we face in the quest to improve treatments for diseases such as prostate cancer and squamous cell carcinoma, is how we can get the immune system to respond in the way we need it to - to stop tumour growth. On the other hand, in conditions such as type 1 diabetes and transplant rejection, the immune system is over-active. If we can find ways to prevent the immune response that leads to the death of insulin-producing cells we could find a new way to treat diabetes. Likewise, if we can prevent the immune system of a transplant patient recognising and reacting to a 'foreign' donated organ, we may be able to improve long-term transplant success."
The cells researchers will be focusing on are:
- gamma delta T cells in the fight against prostate cancer tumour development
- chimaeric antigen receptor-grafted T cells for squamous cell carcinoma
- islet-specific Treg cells for type 1 diabetes
- hepatocyte specific Treg cells for autoimmune liver disease
- alloantigen-specific Treg cells in organ transplantation.
These cells have been selected as targets because scientific research has already shown their importance to the underlying biological processes involved in the development of these diseases.
Working with blood samples, the researchers aim to find ways to extract these cells, activate them or gene modify them in sufficient quantities to provide effective treatments. They will seek to identify methods to achieve this in a laboratory setting, and then to assess whether they can safely control and manage the manufacture of these novel cell-based therapies so they can be tested in patients. By taking this step-by-step approach, they will assess the clinical feasibility of using these 'enhanced' cells as therapeutic agents and put those believed to be most effective forward for clinical trials.
Key to the success of this programme will be the application of leading-edge cell selection systems and use of new Good Manufacturing Practice (GMP) premises within the Clinical Research Facility at Guy's Hospital, which is due to open next year, along with the GMP facility already operating at King's College Hospital.
Professor Frank Nestle, Director of the Clinical Research Facilities said: "We need to find ways to replicate procedures that work in the laboratory in a clinical setting, so that the cells can be manufactured safely in the quantities we need to test them in patients. We look forward to doing this within our hospital environment, in state-of-the-art facilities that are being purpose-built for innovative clinical research."
This research programme is an exciting endeavour for the comprehensive Biomedical Research Centre and for King's Health Partners, one of only five accredited Academic Health Science Centres in the UK, involving King's College London, and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts.
Professor Robert Lechler, Director of King's Health Partners, said: "This research programme will potentially lead to King's Health Partners being among the first to test novel 'enhanced' cell therapies in patients. This is just the kind of translational research that is central to the work of the Biomedical Research Centre and to King's Health Partners – research that depends on the active participation of local patients. We certainly benefit hugely from their involvement and they will be the first to benefit from our progress."
The comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, is one of five National Institute for Health Research (NIHR) comprehensive Biomedical Research Centres in the UK. With its strong focus on 'translational research' across seven research themes and a number of cross-cutting disciplines, it aims to take advances in basic medical research out of the laboratory and into the clinical setting to benefit patients at the earliest opportunity. Access to the uniquely diverse patient population of London and the south east enables it to drive forward research into a wide range of diseases and medical conditions. Website: www.biomedicalresearchcentre.org
Guy's and St Thomas' provides around ¾ million patient contacts in acute and specialist hospital services every year. As one of the biggest NHS Trusts in the UK, it employs over 9,000 staff. The Trust works in partnership with the Schools of Medicine, Dentistry, Nursing and Biomedical Sciences of King's College London and other Higher Education Institutes to deliver high quality education and research. Website: www.guysandstthomas.nhs.uk.
King's College London is one of the top 25 universities in the world (Times Higher Education 2008) and the fourth oldest in England. A research-led university based in the heart of London, King's has 19,700 students from more than 150 countries, and 5,400 employees. An investment of over £500 million has been made in the redevelopment of its estate in recent years
King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services.
The driving purpose of King's Health Partners is to continually seek and bring about swifter and more effective improvements in health and well-being for patients in London and people everywhere. Combining the best of basic and translational research, clinical excellence and world-class teaching to deliver groundbreaking advances in physical and mental healthcare. For more information, visit: www.kingshealthpartners.org