CAR T-cell therapy shows early promise in severe lupus
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Early results from a UCL- and UCLH-led clinical trial suggest that a type of CAR T-cell therapy—developed by Autolus Therapeutics, a UCL spinout—could offer a new treatment approach for people with severe, treatment-resistant lupus. The findings, presented at the EULAR European Congress of Rheumatology (EULAR 2026), come from the ongoing Phase I CARLYSLE study, which is evaluating obecabtagene autoleucel (obe-cel) in patients with severe refractory systemic lupus erythematosus (SLE). The early data indicate that the therapy has a favorable safety profile and may lead to meaningful improvements in disease activity.
Lupus is a chronic autoimmune disease in which the immune system attacks healthy tissues, causing widespread inflammation and damage to organs such as the kidneys, lungs and heart.
It affects at least 5 million people worldwide—about 90% of them women. In its most severe form, known as refractory lupus, patients do not respond to standard treatments, highlighting a significant unmet medical need.
CAR T-cell therapy works by reprogramming a patient's own immune cells to target specific cells in the body and is a successful treatment in many blood cancers. In this case, obe-cel is designed to target CD19-positive B cells, which play a central role in lupus. By depleting these cells, including antibody-producing plasmablasts, the therapy aims to effectively "reset" the immune system.
The CARLYSLE study enrolled patients ages 12 to 65 with active, severe disease who had not responded to multiple standard treatments. Participants received a single infusion of obe-cel following lymphodepletion, at one of two dose levels.
As of November 2025, nine adult patients had been treated. All had highly active disease at baseline, and most were affected by lupus nephritis, a serious complication involving the kidneys.
One of the key findings so far is the therapy's favorable safety profile. Researchers observed no cases of immune effector cell-associated neurotoxicity syndrome (ICANS), a serious neurological side effect sometimes associated with CAR T-cell therapies. There also was no moderate or severe cytokine release syndrome (CRS)—an inflammatory response sometimes triggered by immunotherapy.
There was one dose-limiting toxicity involving liver injury, which fully resolved. Other side effects, including neutropenia and infections, were consistent with expectations for CAR T-cell therapy and were considered manageable.
The absence of severe CRS or neurotoxicity is particularly encouraging and may reflect obe-cel's design, which incorporates features intended to reduce immune-related toxicity.
Alongside this reassuring safety profile, researchers observed encouraging signs of clinical benefit.
In the lower-dose group, 5 of 6 patients achieved remission according to standard lupus criteria, with responses emerging within a few months of treatment. Patients also experienced rapid improvements in disease activity scores, as well as reductions in key disease markers such as anti-double-stranded DNA antibodies and increases in complement levels.
For patients with kidney involvement, there were additional positive signals. Several achieved complete or partial renal responses, with reductions in proteinuria and stabilization, or improvement, of kidney function over time.
Although follow-up in the higher-dose group remains shorter, early observations are consistent with these findings.
Following infusion, patients showed strong expansion of CAR T cells and deep depletion of B cells. Over time, B cells began to return, typically between three and six months, but were predominantly early-stage (transitional and naïve) cells, rather than the more mature populations associated with autoimmune activity.
This pattern suggests that the therapy may be enabling an "immune reset," rather than simply suppressing the immune system—an important objective in treating autoimmune diseases such as lupus.
Dr. Claire Roddie, an investigator on the trial from UCL Cancer Institute and a UCLH consultant hematologist, 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 therapy used in this trial, called AUTO1/obe-cel, was developed at UCL by a team led by Professor Martin Pule (UCL Cancer Institute) for the treatment of blood cancers such as leukemia. But the concepts on which CAR-T therapies are based—namely, interrupting the immune cells attacking healthy tissues—have been researched at UCL for more than two decades.
While these findings are preliminary and based on a small number of patients, they highlight the potential of CAR T-cell therapy as a novel approach for severe lupus.
Dr. Maria Leandro, an investigator on the trial from UCL Division of Medicine and a consultant rheumatologist at UCLH, said, "This trial builds on the research that our team at UCL and UCLH rheumatology has been conducting for the past 25 years on the benefits of killing B cells in some autoimmune diseases. This kind of innovative research work only becomes possible with close collaboration from teams in rheumatology, renal medicine and hematology."
Researchers at UCL and collaborating centers continue to follow patients in the CARLYSLE study to better understand the durability of responses, optimal dosing and long-term safety.
Obe-cel is also being investigated in patients with severe, refractory SLE with active lupus nephritis in the Phase II LUMINA trial (NCT07053800), with recruitment ongoing at eight sites in the U.K.
If confirmed in larger trials, obe-cel could represent a new treatment paradigm for patients with severe, treatment-resistant SLE.
The trial is led by UCL and University College London Hospitals NHS Foundation Trust (UCLH) and is sponsored by Autolus, with support from the National Institute for Health and Care Research UCLH Biomedical Research Center. There are three participating sites, with Manchester recruiting the first patient nationally at the National Institute for Health and Care Research (NIHR) Manchester Clinical Research Facility (CRF) at Manchester Royal Infirmary (MRI).
Key medical concepts
Systemic lupus erythematosusCAR T Cell TherapyLupus Nephritis
Clinical categories
Rheumatology Provided by University College London Who's behind this story?
Lisa Lock
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