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Alloantigen-specific Treg cells targeted for organ transplantation

Published on September 3, 2009 at 1:00 AM · No Comments

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.

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