World-first gene therapy to target devastating rare immune disorder

NHSBT's Clinical Biotechnology Centre is playing a key role in first-of-its-kind gene therapy to treat people with CTLA-4 insufficiency, a rare and life-limiting inherited immune disorder.

The work is being advanced through a collaboration supported by LifeArc, a self-funded medical research organisation, and developed by scientists at University College London (UCL), with manufacturing support from NHS Blood and Transplant (NHSBT) and Great Ormond Street Hospital (GOSH).

CTLA-4 insufficiency is a rare genetic condition that disrupts how the immune system is controlled. Patients can develop a range of symptoms, from bowel inflammation to changes in the numbers of different types of blood cells, which can lead to recurrent infections and significantly reduced life expectancy.

Current treatments focus on managing these symptoms. In some cases, a bone marrow transplant may offer the hope of a cure but comes with significant risks and are not always possible.

This new therapy takes a different approach by replacing a faulty gene in a patient's own immune cells. In the lab, scientists can use a tool, often called 'molecular scissors' (CRISPR/Cas9), to remove the faulty gene and replace it with a healthy one. The corrected cells are then returned to the patient to help restore normal function.

Early pre-clinical studies have shown encouraging results, with corrected cells demonstrating improved control of immune activity. The programme will now move through further development ahead of a clinical trial in up to 8 patients expected to begin in 2028.

Manufacturing and translational development is being supported by NHSBT’s Clinical Biotechnology Centre in Bristol, part of the LifeArc and Medical Research Council-funded Innovation Hubs for Gene Therapies network, which provides specialist capabilities to accelerate patient access to advanced genetic medicines.

NHSBT will manufacture the AAV6 viral vector used to deliver the corrected gene into the patient's T cells. Great Ormond Street Hospital (GOSH) will manufacture the final cell therapy product and act as sponsor of the clinical trial. GOSH, UCLH and the Royal Free Hospital are expected to serve as clinical sites for patient treatment.

Statements about the therapy

Commenting on the new therapy, Sam Barrell, CEO at LifeArc, said:

"This is an important milestone in advancing a truly innovative therapy for a life-limiting rare disease. By supporting this research, we hope to help accelerate the development of an approach that aims to address the underlying cause of the condition, rather than simply manage its symptoms."

Dr Paul Lloyd-Evans, Head of the NHSBT Clinical Biotechnology Centre, said:

"We’re working at the cutting edge of research, using our advanced manufacturing capability to enable complex gene and cell therapies. Producing high-quality viral vectors is a critical step in ensuring safe and effective translation into clinical trials. By supporting this world-leading trial, we hope to save and improve even more lives."

Dr Susan Walsh, CEO at Immunodeficiency UK, said:

"Living with an immunodeficiency like CTLA 4 insufficiency can affect every part of family life, and patients urgently need better options. For our community, this ground-breaking research represents more than scientific progress. It offers hope that the condition could one day be treated at its root."