The first UK patients have received a pioneering immunotherapy treatment for the most severe type of lupus through a clinical trial led by University College London (UCL) and University College London Hospitals NHS Foundation Trust (UCLH).
This Phase 1 international trial, named CARLYSE, is the UK’s first to evaluate CAR-T (Chimeric Antigen Receptor T-cell) therapy for a condition beyond cancer.
Involving 12 patients with lupus, also known as systemic lupus erythematosus (SLE), from various countries, the trial focuses on this chronic autoimmune disorder, where the immune system mistakenly attacks the body’s healthy tissues.
Previously, CAR-T therapy has primarily been applied to cancer treatment. This approach extracts a patient’s T-cells (a type of white blood cell), then genetically alters them to target and destroy specific harmful cells—especially B cells, which are known to produce antibodies.
Since B cells play a significant role in lupus, researchers believe CAR-T therapy may be effective for treating the condition as well.
Researchers of the study anticipate the possibility that this single CAR-T treatment could greatly reduce, or even eliminate, the need for long-term medications in patients with severe lupus.
The study, sponsored by Autolus, is led by UCL and UCLH, with three sites participating. The first patient was recruited nationally at the National Institute for Health and Care Research (NIHR) Manchester Clinical Research Facility (CRF) at Manchester Royal Infirmary (MRI).
Dr Maria Leandro, who is an investigator on the trial from UCL Division of Medicine as well as a Consultant Rheumatologist at UCLH, explained “This trial builds on the research UCL and UCLH rheumatologists have been conducting for the past 25 years on the benefits of killing B cells in some autoimmune diseases. We have seen the effectiveness of CAR-T in cancer, particularly blood cancers, and hope we can replicate this in autoimmune diseases, starting with lupus.
“Our early phase trial aims to recruit 12 people worldwide and we hope to replicate the results of a small German trial which showed an improvement in lupus patients treated with CAR-T cell therapy. This kind of innovative research work only becomes possible with close collaboration from teams in rheumatology, renal medicine and haematology.”
Researchers highlighted the fact that in the UK, approximately 69,000 people are affected by lupus, with about 90% of cases occurring in women. The severity of the disease varies from mild to life-threatening, demonstrating the need for the study and findings.
While various medications can help manage symptoms and reduce the risk of organ damage, they can sometimes cause unwanted side effects or lose effectiveness over time.
Professor Ben Parker, Consultant Rheumatologist at the Kellgren Centre for Rheumatology and lead researcher on the study at the MRI within Manchester University NHS Foundation Trust (MFT), indicated that they are thrilled to be the first in the UK to conduct this groundbreaking research, which they hope will transform treatment for high-risk lupus patients and could even pave the way for a cure.
Professor Parker further indicated that Lupus requires lifelong treatment, but this new therapy has the potential to change that, which is incredibly promising.
The preparation and administration of CAR-T products is a complex process, demanding specialized expertise in rheumatology, oncology, and clinical trial management, typically taking several weeks to complete.
The therapy tested in this trial, known as AUTO1/obe-cel, was created at UCL by Professor Martin Pule’s team (UCL Cancer Institute) to treat blood cancers such as leukemia. However, the foundational concepts behind CAR-T therapies—primarily the idea of halting immune cells from attacking healthy tissues—have been under investigation at UCL for over 20 years.
Dr. Claire Roddie, a trial investigator from UCL Cancer Institute and Consultant Haematologist at UCLH, indicated that it is wonderful to be part of the broader development of the ‘low toxicity’ CAR-T therapy, innovated at UCL, for patients with refractory lupus.
