A woman in Manchester is the first person in the UK to receive an innovative treatment for the most serious form of lupus – an autoimmune condition which can cause damage to the heart, lungs, joints, brain or kidneys.
Researchers hope that the one-off CAR-T (Chimeric Antigen Receptor T-cell) therapy will reduce, or even remove, the need for life-long medication for patients with severe lupus.
The international Phase 1 study, called CARLYSE, is the first in the UK to assess the potential of CAR-T therapy to treat a disease other than cancer.
It is led by University College London Hospitals NHS Foundation Trust (UCLH) and UCL and 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).
Lupus (systemic lupus erythematosus, or SLE) is a long-term condition which occurs when the body’s own immune system attacks healthy parts of the body, which can be life-threatening. Although there are different drugs that can help relieve many of the symptoms from mild to severe, and reduce the chances of organ damage, these drugs can have unwanted side-effects and can even stop working.
Approximately 69,000 people in the UK have lupus. The causes of lupus are not fully understood and there is currently no cure for the condition. Side effects can include joint and muscle pain, skin rashes and extreme tiredness.
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.”
Lupus is an uncommon condition with around 90 per cent of cases occurring in women. The condition tends to appear between the ages of 15 and 50 and is more common in people with an African, Caribbean, Asian or Chinese background.
UCLH Consultant Rheumatologist and Honorary Associate Professor at the UCL Division of Medicine, Dr Maria Leandro 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.”
Professor Parker, who is also Medical Director of the NIHR Manchester CRF at MRI and Co-Director of the NIHR Manchester CRF, added: “This novel treatment has been a collaborative effort across multiple specialities at MFT, involving rheumatology, haematology, cancer services and Manchester CRF’s experimental Phase 1 clinical trial expertise. This ground-breaking new therapy marks a significant milestone in our research into lupus and offers real hope to our patients in Manchester and beyond.”
UCLH Consultant Haematologist and UCL Cancer Institute researcher Claire Roddie said: “It is fantastic to be involved in the wider development of the UCL-innovated, ‘low toxicity’ CAR-T therapeutic AUTO1/obe-cel for patients with refractory lupus.
“In early phase trials of patients with blood cancers we showed that AUTO1/obe-cel was well tolerated and resulted in durable remissions in substantial numbers of patients. We are hopeful that AUTO1/obe-cel 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.”
Dr Eleni Tholouli, Consultant Haematologist and Director of the Adult Stem Cell Transplant and CAR-T Unit at MRI, and Sub Investigator of the study, said:
“We have been delivering cutting-edge CAR-T therapy to cancer patients at MFT since 2018, and we have seen remarkable benefits to patients and results during this time.
“It is an incredibly exciting time to now offer this mode of treatment to lupus patients through this clinical trial, which we hope will provide positive outcomes and revolutionise treatment options for patients with the disease.
“I am incredibly proud to be part of this exciting research journey and it has been a real team effort to deliver this complex investigational therapy. For us at MFT, this is the first trial to be co-delivered by rheumatology and haemato-oncology teams and marks a real step forward in how we are utilising our expertise at MFT to deliver ground-breaking research for the benefit of our 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.