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Patients' Own Cells could be Key to Treating Crohn's Disease



LONDON (UK), February 2019 — A new technique using patients' own modified cells to treat Crohn's disease has been proven to be effective in experiments using human cells, with a clinical trial of the treatment expected to start in the next six months.

Researchers at the NIHR Guy's and St Thomas' Biomedical Research Centre (BRC) developed the technique by studying white blood cells taken from patients who have Crohn's disease and comparing them to cells of healthy people. Their findings allowed cell therapy specialists in the BRC to develop a treatment involving taking patients' cells, and growing them in a special culture so that they behave more like cells from healthy people.

The research, published in Gastroenterology, shows that this technique is effective in human cells, meaning it is ready for use in a clinical trial. The proposed Tribute Trial will test whether the treatment is safe and effective for treating Crohn's disease.

Crohn's disease is a lifelong condition in which parts of the digestive system become severely inflamed, causing a range of symptoms such as diarrhea, stomach aches, tiredness and weight loss. Its causes are unknown, but the immune system is known to play a part.

Graham Lord, FRCP, Ph.D., previously director of the NIHR Guy's and St Thomas' BRC and now vice president and dean of the faculty of biology, medicine and health at the University of Manchester, led the research. "This is the next frontier in cell therapy as we're going beyond treating the symptoms of Crohn's disease and trying to reset the immune system to address the condition,” he said. "It's a real home-grown treatment in the sense that we started with observing cells and tissues donated by patients at Guy's and St Thomas', have developed a treatment and are now starting to undertake trials, all at the Trust.

“It shows how central patients are to research, helping to create a treatment that might help thousands more people."

The researchers found that regulatory T cells from Crohn's patients produced less of a gut-specific protein called integrin α4β7 than regulatory T cells from healthy people. Working with the specialists at the NIHR Guy's and St Thomas' BRC's Advanced Therapies Manufacturing Platform, they developed a cell therapy technique based on these findings.

The technique involves developing cells from the Crohn's disease patients with a molecule called RAR568, which restores healthy levels of integrin α4β7. The cells are then given back to patients by intravenous infusion.

Peter Irving, M.D., FRCP, a consultant gastroenterologist and co-author on the paper, said, "While the treatments available for Crohn's disease have increased over recent years, they only work in some patients. In addition, the treatments have potentially serious side effects in some patients. This research paves the way for a trial of using patients' own cells to treat their Crohn's disease and we look forward to offering people the chance to take part in the very near future."

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DOI: 10.1053/j.gastro.2019.01.025