King’s College Hospital and King’s College London are trialling cutting-edge cell therapy to develop a brand new treatment for the condition. It’s a world first - funded by The Aplastic Anaemia Trust and LifeArc.

On 7th December, Dr Nazia Matto, the trial’s lead GMP production scientist presented initial findings from the TIARA trial, revealing promising results in a presentation at the American Association on Haematologists (ASH) conference in San Diego.

This stage one trial is investigating the safety and tolerability of expanded autologous regulatory T cells (immune cells, also referred to as Tregs) in treating patients with aplastic anaemia. The early results have confirmed that that Tregs from AA patients are expandable, safe to infuse and may dampen immune system abnormalities associated with the condition.

Dr Nazia Matto (right) in the lab where the Treg treatment is prepared, with Research Assistant, Marta Rzepkowska.

Our readers will know that aplastic anaemia is a rare and life-threatening blood disorder that occurs when the bone marrow fails to produce enough red blood cells (responsible for carrying oxygen around the body), white blood cells (which help fight infection), and platelets (responsible for clotting after bleeding).

TIARA trial participants are given two infusions of their own expanded autologous Tregs – a type of cellular therapy – to treat the condition, and will be monitored for two years. Three of the treated patients had been diagnosed with severe AA, two with non-severe, and one with Very Severe AA.

Tregs were successfully expanded from all six patients and all have completed the treatment with both doses. Five patients did so without any safety concerns. One patient developed antibiotic-responsive low-grade fever within 24 hours of the first infusion but received the second dose without any side effects.

A year on from one trial participant’s treatment, they have gone from being transfusion-dependent to no longer requiring transfusions. Another patient also showed improvements, with red cell transfusion independence lasting 100 days.

This first-of-its-kind trial is funded by LifeArc and The Aplastic Anaemia Trust, and is managed by King’s Health Partners Haematology – a pioneering collaboration between three NHS Foundation Trusts in London with the academic expertise of King’s College London.

How the treatment works

Regulatory T cells (Tregs) are white blood cells that have a role in regulating or modulating the immune responses against cells of our body to prevent disease or ‘autoimmune hit’ where the cells of the immune system attack the bone marrow stem cells. We aim to collect, expand and grow the patient’s own Tregs to harness the beneficial effects at controlling the auto-immune attack.

In this trial we aim to discover whether a patient’s own Tregs can be modified to treat Aplastic Anaemia – a condition that can have a huge impact on a person’s life – and determine whether healthy bone marrow stem cells recover, thereby improving patients’ blood count.

This type of treatment has shown promising signs in other conditions and we hope to build upon existing research to benefit those with Aplastic Anaemia.

Dr Shreyans Gandhi, Consultant Haematologist at King’s College Hospital and Principal Investigator of the TIARA trial.

Aplastic anaemia is a condition that desperately needs new treatments. Our work in rare disease aims to remove barriers and accelerate the pace with which treatments reach the people who need them, so, I am delighted that our investment here has helped do just that. I look forward to hearing how the trial progresses.

 

Dr Catriona Crombie, LifeArc’s Head of Rare Disease Research 

There is an urgent need for new treatments to offer patients a better chance of survival and improve their quality of life.

The TIARA trial - the first to use high doses of Tregs in two doses, two weeks apart - is based on six years of pioneering work at King's College London in which it was discovered that Tregs were abnormal and reduced in numbers in patients with Aplastic Anaemia.

 

Professor Ghulam Mufti, Chief Investigator of the TIARA trial, and Chair of The Aplastic Anaemia Trust’s Research and Clinical Advisory Panel