Cancer therapy with potential to transform lupus treatment delivered in UK first

CAR T cells - Closeup view 3d illustration
CAR T cells - Closeup view 3d illustration

The first UK patients have received an innovative immunotherapy to treat the most serious form of lupus, as part of a clinical trial led by UCL and UCLH.

The international Phase 1 study, called CARLYSE, is the first in the UK to assess the potential of CAR-T (Chimeric Antigen Receptor T-cell) therapy to treat a disease other than cancer.

The trial will involve 12 patients from around the world who have lupus (systemic lupus erythematosus, or SLE), a long-term condition that occurs when the immune system attacks healthy parts of the body.

Currently, CAR-T therapy has most commonly been used to treat cancer. The process involves removing a patient’s T white blood cells and genetically modifying them to recognise and attack problem-causing cells, in particular B cells (a type of white blood cell that create antibodies).

However, because B cells are a major factor in lupus as well, researchers have proposed that CAR-T could also be used to treat this condition.

Researchers hope that the one-off CAR-T therapy will reduce, or even remove, the need for life-long medication for patients with severe lupus.

The trial is led by UCL and University College London Hospitals NHS Foundation Trust (UCLH) and is sponsored by Autolus. 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).

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 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."

Approximately 69,000 people in the UK have lupus, with around 90% of cases occurring in women. which ranges from mild to severe and can be life-threatening.

Although there are different drugs that can help relieve many of the symptoms and reduce the chances of organ damage, these drugs can have unwanted side-effects and can stop working.

Professor Ben Parker, Consultant Rheumatologist at the Kellgren Centre for Rheumatology and study lead at the MRI, part of Manchester University NHS Foundation Trust (MFT), said: "We are delighted to be the first to deliver this fantastic research in the UK, which we hope will revolutionise treatment for patients with high-risk lupus, that could potentially lead to a cure for the disease.

"Lupus is a disease that requires life-long medication, but this therapy has the potential to change that, which is incredibly exciting."

Preparation and delivery of CAR-T products is complex, requiring expertise across rheumatology, oncology and clinical trial delivery, a process which is completed over several weeks.

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 leukaemia. But the concepts upon which CAR-T therapies are based, namely interrupting the immune cells attacking healthy tissues, have been researched at UCL for over two decades.

Dr Claire Roddie, an investigator on the trial from UCL Cancer Institute and a UCLH Consultant Haematologist, said: "It is fantastic to be involved in the wider development of the UCL-innovated, ’low toxicity’ CAR-T therapeutic for patients with refractory lupus.

"In early phase trials of patients with blood cancers we showed that the therapy was well tolerated and resulted in durable remissions in substantial numbers of patients. We are hopeful that it will have a similarly transformational impact in patients suffering the debilitating symptoms of refractory lupus and it is hugely exciting to be able to offer this novel treatment to our lupus patients."

Patient case study: Katherine’s story

32-year-old Katherine was the first person in the UK to receive the CAR-T lupus therapy, at the National Institute for Health and Care Research (NIHR) Manchester Clinical Research Facility (CRF) at Manchester Royal Infirmary (MRI) in July this year.

Katherine has been a patient of Professor Parker since her lupus diagnosis in 2021 at the Kellgren Centre for Rheumatology, based at MRI. She was invited to take part in the CAR-T lupus therapy research after several drugs (steroids and immunosuppressants), failed to ease her symptoms.

Katherine who lives in Manchester, said: "When Professor Parker told me about the research, I was excited, but I couldn’t believe it. When you speak about lupus you don’t talk about the possibility of coming off medication. However, nothing had worked permanently for me. All the drugs, even when taken at high doses, had just offered temporary relief and nothing really helped with the pain. I thought this could be a solution I never thought possible.

"I’d lived a normal life until my late 20s, but getting lupus turned my life upside down. I had to give up my job in banking. I had difficulty just getting out of bed, climbing the stairs and even doing day-to day tasks. I was forced to adapt to living life in a different way.

"I cried happy tears going home from that appointment, thinking that there was a chance I could wake up every morning without pain, being able to do things like play with my daughter, and imagining all the possibilities of living a somewhat normal life - it felt amazing."

Katherine had been living with constant joint pain, extreme fatigue, inflammation, and a weakened immune system.

Approximately six weeks after receiving the CAR-T therapy Katherine said: "Even though I wasn’t expecting to feel this better so quickly, I do feel I have more energy and I have had no joint swelling. I’m feeling hopeful for the future.

"I’d say to anyone given the chance to take part in this research, definitely take part because not only could you benefit yourself, but you could be helping to find a ground-breaking treatment for thousands of other people, not just with lupus, but with related conditions." 

Katherine will undergo regular checks at Manchester CRF at the MRI for around two years with a 15-year follow up study to understand the long-term effects of the treatment.

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