CAR-T therapy for severe lupus shows promise in early trial

Early results from an ongoing Phase I clinical trial suggest that a single dose of CAR T-cell therapy may benefit patients with severe, treatment-resistant lupus.

Lupus is a chronic autoimmune condition characterised by widespread inflammation that can damage organs including the kidneys, heart and lungs. There is currently no cure, and some patients do not respond adequately to standard immunosuppressive treatments. Now, researchers at University College London (UCL) and UCL Hospitals (UCLH) have reported interim findings from a multi-centre clinical study called CARLYSLE, recently presented at the EULAR European Congress of Rheumatology. The approach – a CAR T-cell therapy developed by Autolus Therapeutics – has led to remission in five of the first nine patients with treatment-resistant systemic lupus erythematosus (SLE).

'These findings provide early evidence that CAR T-cell therapy may be able to reset the immune system,' said Dr Claire Roddie, consultant haematologist at UCLH and co-investigator on the trial. 'Although these are still early days, the results mark an important step forward in exploring how cellular therapies could transform the treatment of autoimmune diseases.'

CAR T-cell therapies were originally developed to treat certain blood cancers and involve genetically modifying a patient's own T-cells so they can recognise and destroy specific target cells (see BioNews 1131, 1231, 1323 and 1338). In lupus, certain B-cells produce antibodies that mistakenly attack healthy tissues. The CAR T-cell therapy used in CARLYSLE, known as obe-cel, relies on reprogramming T-cells so that they can attack the B-cells that play a central role in lupus. The modified T-cells are infused back into the patient, where they can deplete B-cell populations and reduce the autoimmune response driving disease.

The CARLYSLE trial, launched in 2024, is evaluating the safety and preliminary efficacy of obe-cel in people with severe lupus who have not responded to existing therapies. Researchers hope it will help determine whether CAR T-cell therapy could offer a new treatment option for patients with difficult-to-treat disease.

People aged 12–65 years with severe, treatment-resistant SLE were enrolled in the early-stage, uncontrolled trial. As of November 2025, nine patients had received an infusion of obe-cel following a short course of chemotherapy that reduces the risk of the modified T-cells being rejected by the body.

Among the first six patients treated at the lower-dose level, five achieved clinical remission within months of treatment, alongside rapid reductions in disease activity and improvements in laboratory markers associated with lupus. Some participants were also able to reduce or discontinue immunosuppressive medications. Patients treated at the higher dose level have been followed for a shorter period, but early findings appear broadly consistent with those seen in the lower-dose group.

'My whole system was affected by lupus and my joints were so painful that sometimes I couldn't walk. My kidneys, heart and lungs were all getting worse,' explained Katie Tinkler, one of the first NHS patients to receive obe-cel in the CARLYSLE study. 'Now I don't have these problems anymore. It's miraculous for me. My life two years ago versus now, it's unrecognisable.'

Although the findings are encouraging, the study remains small and lacks a control group, meaning larger and longer-term trials will be needed to confirm the therapy's safety and effectiveness.

'These findings are truly groundbreaking and offer fresh hope to people living with lupus,' said Professor Karl Peggs, director of the UCLH Biomedical Research Centre. 'If these results are confirmed in larger studies, the prospect of a cure for lupus may no longer be out of reach.'

Obe-cel is also being evaluated in other early-phase clinical trials across oncological, autoimmune and neurological diseases, including studies in progressive multiple sclerosis, severe lupus nephritis and paediatric B-cell leukaemia and lymphoma.