A new treatment which involves growing a patient's immune cells and then infusing them back into their body has shown promise for people with the rare blood disorder aplastic anaemia.
Results from the Phase I trial, led by Professor Ghulam Mufti, provides the first evidence that autologous regulatory T-cell therapy is feasible and safe in people with aplastic anaemia, and may have clinical benefit.
Aplastic anaemia (AA) is an autoimmune bone marrow failure disorder. It occurs when the immune system attacks blood-forming stem cells in the bone marrow, causing dangerously low blood counts. Standard treatment with strong immunosuppressive drugs is associated with considerable side effects, and up to a third of the patients don't respond to them. Those who do respond may relapse and require long-term immunosuppressive medications.
Previous research from Professors Mufti and Shahram Kordasti has shown that patients with AA have reduced numbers and impaired function of regulatory T cells (Tregs) - immune cells that normally suppress harmful autoimmune responses. Tregs act as the immune system's brakes, with the primary goal of preventing autoimmune attacks, suppressing excessive inflammation and maintaining immune tolerance. In AA, problems with a person's Tregs allow destructive immune responses against bone marrow stem cells.
The researchers sought to test whether it was possible to safely take Tregs from a patient, grow billions more in a special laboratory, and infuse them back to restore immune regulation.
Six people with severe or treatment-resistant AA were recruited to the trial by Dr Shreyans Gandhi (consultant haematologist at Kings College Hospital). The researchers removed and filtered some of their blood to separate white blood cells with Tregs. Dr Nazia Mattu and her colleagues produced billions of Tregs for each patient in a Good Manufacturing Practice (GMP) laboratory at Guy's Hospital. Two infusions were administered to the patients, two weeks apart.
The study met its primary goal of confirming that the treatment was safe, with no serious treatment-related adverse events. Three patients experienced meaningful clinical benefit and remain independent of red cell or platelet transfusions.
This first-in-humans phase 1 trial shows that expanded autologous Tregs are safe to administer and produce favourable clinical responses in patient's refractory to standard therapeutic options."
Ghulam Mufti, Emeritus Professor, King's College London
One of the most important scientific findings was that the researchers could track the infused Tregs after treatment. Using techniques such as mass cytometry, they observed that Tregs peaked around day 28 and were still present in the bone marrow 6 months after treatment. This is important because it means the cells persist for long enough to exert their effects.
The results suggest this treatment could have a clinically meaningful benefit for patients with AA, particularly those who are resistant to conventional therapy or are elderly and unable to tolerate conventional therapy. The results from this study could have wider implications for the treatment of other autoimmune diseases.
The trial was funded by LifeArc and the Aplastic Anaemia Trust (AAT).
