Pioneering cell therapy trial for severe autoimmune disease starts

The Oxford Experimental Medicine Clinical Research Facility (EMCRF) has recruited its first patients into an early-phase study of an innovative cell therapy for severe autoimmune disease.

Sponsored by Quell Therapeutics, the CHILL trial will investigate a new engineered nTreg therapy for conditions including rheumatoid arthritis and systemic sclerosis (scleroderma). It is the first time Oxford has delivered an engineered cell therapy trial for autoimmune disease outside a haematology-oncology setting.

Two participants were recruited at Oxford University Hospitals (OUH) NHS Foundation Trust after a first person was dosed at Leeds Teaching Hospitals NHS Trust.

Regulatory T cells, or Tregs, are specialised immune cells that help prevent the immune system from attacking the body's own tissues and keep inflammation under control.

Quell Therapeutics has engineered these cells with a CD19 B-cell activated receptor, creating a therapy designed to travel to sites of inflammation, restore immune balance and reduce the harmful immune activity that drives disease.

Within the NHS there is experience delivering early-phase Advanced Therapy Investigational Medicinal Products (ATIMP) for oncology, but there is limited experience in other settings such as autoimmunity.

A coordinated approach involving Quell Therapeutics, the UKCRF Network and participating facilities, including the Oxford (EMCRF), part of the National Institute for Health and Care Research Clinical Research Facility: Oxford, the NIHR Industry Hub and partners across the UK life sciences ecosystem helped accelerate the set-up of the trial and prepare the study to begin recruiting participants.

To support delivery of the study, new and innovative patient pathways had to be developed locally. Working with OUH’s Clinical Haematology department and its Advanced Cellular Therapy (ACT) team has been fundamental to ensuring the study could be delivered safely. Alongside this, OUH’s Pharmacy Clinical Trials Unit and the ACT pharmacy team have been working closely on logistics for receiving, storing and preparing the cell product to be administered.

Cushla Cooper, Clinical Operational Lead for the Oxford EMCRF, said: “ATIMP trials have traditionally been delivered in haematology and oncology. For the first time at Oxford, we are delivering an engineered nTreg trial for autoimmune disease outside these specialities.

“Administering the cell therapy to our first patient was a significant milestone for the study team. We are only the second site globally to do so. After many forms, and rigorous safety checks along the way, the patient received their dose, which took around 10 minutes. The nursing team reported the patient tolerated it well and was discharged home the following day.”

Joe Browning, OUH Clinical Lead for Haematology, commented: “We are delighted to work with our colleagues at the EMCRF on the CHILL trial and are very pleased that the first OUH patient has now been treated. In haematology we are very aware that cellular therapies are moving beyond purely haematological indications and we are keen to support the delivery of these treatments. This necessitates close working with colleagues in different specialties, and sharing the significant medical, nursing and pharmacy expertise which we in haematology have developed over many years using cellular therapies in our routine practice”.

Chief Investigator for the CHILL study and Director of the NIHR CRF: Oxford, Professor Christopher Buckley, said: “People living with rheumatoid arthritis and systemic sclerosis dream of a cure. CAR-T cells, which kill disease-causing cells, have emerged as therapies that may help reset damaged tissues. But CAR-T cells kill; they do not regulate. We believe engineered nTregs - natural regulators of tissue immune responses - could achieve safe, deep and durable disease control and move us closer to the prospect of a cure.”