A pioneering clinical trial led by UCLH and UCL is showing early promise for people with severe lupus who have exhausted existing treatment options.
Early results from the ongoing Phase I CARLYSLE trial supported by the BRC have been encouraging. As of November 2025, nine adults with severe, treatment-resistant lupus had received the treatment. All had highly active disease despite multiple previous therapies, and most had lupus nephritis, a serious form of the disease that affects the kidneys.
Researchers found that five of the first six patients treated at the lower dose achieved remission according to standard lupus criteria, with improvements emerging within months of treatment. Patients also experienced rapid reductions in disease activity, alongside improvements in important laboratory markers associated with lupus.
For patients whose kidneys had been affected by the disease, the results were particularly encouraging. Several achieved complete or partial renal responses, with reductions in proteinuria and stabilisation or improvement in kidney function over time.
The treatment has also demonstrated a favourable safety profile. Researchers observed no cases of immune effector cell-associated neurotoxicity syndrome (ICANS), a serious neurological side effect associated with some CAR T-cell therapies, and no moderate or severe cytokine release syndrome.
Scientists believe the treatment may be doing more than temporarily suppressing lupus. Following treatment, patients experienced deep depletion of disease-causing B cells. When these cells returned several months later, they were predominantly immature cells rather than the more mature populations associated with autoimmune activity. This suggests the therapy may be helping to reset the immune system itself.
For Katie Tinkler, one of the first patients treated in the study, the experimental CAR T-cell therapy has been life-changing.
Before joining the trial, Katie’s lupus was affecting almost every part of her body. Her kidneys were deteriorating, her lungs were severely inflamed and she had developed myocarditis, making even everyday activities a struggle.
“I literally couldn’t walk from Warren Street tube station to the outpatient department without stopping,” Katie, 52, of Guildford, Surrey, said. “My joints were so painful that it was prohibiting me from living my life, and it was only getting worse.”
Katie had lived with lupus for decades, but in the years leading up to the trial her condition had become increasingly difficult to control despite multiple treatments, leaving her with few remaining options. She was under the care of specialists across rheumatology, haematology, nephrology, cardiology and respiratory medicine.
“My whole system was affected,” she said. “Life was very hard work, and that was 24/7.”
When doctors at UCLH offered her the opportunity to join the CARLYSLE trial, Katie knew the treatment carried significant risks.
“I went in fully aware of the risks,” she said. “But I also knew my body was in such a bad state that something major had to happen if I was going to survive into the next decade of my life.”
The trial is evaluating obecabtagene autoleucel (obe-cel), a type of CAR T-cell therapy originally developed for blood cancers. CAR T-cell therapy works by collecting a patient’s own immune cells, genetically modifying them in a laboratory, and then returning them to the body to target specific cells.
In lupus, the treatment is designed to eliminate CD19-positive B cells, which play a central role in driving the disease. Researchers hope this approach can effectively reset the immune system rather than simply suppress it.
UCLH consultant haematologist and trial co-investigator Claire Roddie said: “For patients living with severe lupus that has not responded to existing treatments, the options can be very limited. These findings provide early evidence that CAR T-cell therapy may be able to reset the immune system and drive meaningful clinical improvements after a single treatment.
“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.”
The treatment process was intensive. After undergoing apheresis to collect her T cells, Katie waited several weeks while they were modified in the laboratory before returning to UCLH for chemotherapy and the infusion of the engineered cells.
The weeks that followed were challenging.
“It was a very lonely time,” she said. “I was very sick with the chemotherapy. My blood pressure was very high and I was having scans every day. It was a really massive thing to undertake.”
Yet even during her recovery, Katie began noticing dramatic changes.
“When I left hospital, I had no joint pain,” she said. “I’ve never had any joint pain since.”
The improvement came remarkably quickly. Before treatment, her hands were so swollen that she struggled with basic tasks. Within weeks, the pain that had dominated her daily life had disappeared.
Eighteen months later, it has not returned.
By six months after treatment, Katie’s lupus markers had returned to normal levels for the first time in more than 30 years.
“That hadn’t happened since 1993,” she said.
The impact has extended far beyond blood test results. Conditions linked to her lupus, including myocarditis, lung inflammation and antiphospholipid syndrome, have resolved, while the number of medications she takes has fallen dramatically.
“There’s no comparison,” she said. “It’s like night and day.”
Today, Katie walks regularly, swims three times a week and spends time gardening. Earlier this year, she returned to skiing for the first time in many years.
“I can participate in life now whereas before I had to watch my family and friends doing physical activities from the sidelines,” she said. “At my daughter’s wedding I danced all night. The summer before, I wouldn’t have been able to do that.”
Katie’s experience reflects the promise researchers are beginning to see across the trial, which builds on more than two decades of research at UCL and UCLH into the role of B cells in autoimmune disease.
UCLH consultant rheumatologist and trial co-investigator Maria Leandro said: “This trial builds on 25 years of research at UCL and UCLH into the role of B cells in autoimmune disease. It demonstrates the importance of collaboration between rheumatology, renal medicine and haematology in bringing innovative treatments to patients.”
While longer follow-up and larger studies will be needed to confirm the results, investigators believe CAR T-cell therapy could represent a fundamentally new approach to treating severe autoimmune disease.
Professor Karl Peggs, Director of the NIHR UCLH Biomedical Research Centre, said: “These findings are truly groundbreaking and offer fresh hope to people living with lupus. While more research is needed, the possibility that CAR T-cell therapy could deliver an immune reset and potentially free patients from the cycle of chronic autoimmune disease marks a remarkable step forward.”
Researchers at UCL and UCLH continue to follow patients in the CARLYSLE study to understand how durable the responses are and to assess long-term safety. A larger Phase II study, LUMINA, is now recruiting patients with severe lupus and active lupus nephritis across multiple UK centres.
Katie hopes her experience offers encouragement to others living with severe autoimmune disease.
“People with autoimmune diseases often accept that they have to live with a chronic illness that’s attacking them 24 hours a day from the inside,” she said.
“For me, it’s been revolutionary.”
Photo: Lucy North/PA
