UCLH announces start of CAR T cell therapy clinical trial for lupus patients

UCLH announces start of CAR T cell therapy clinical trial for lupus patients

Three patients in the UK have received 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.

Katie Tinkler receiving her cell infusion from Nicole Prescott and Rob McDonnell, both senior clinical practice facilitators in haematology at UCLH. Looking on is clinician scientist Claire Roddie, a consultant haematologist and an expert in CAR T cell therapy. Picture: Lucy North/PA

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 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.”

Former fitness instructor ‘beyond excited’ to receive lupus therapy in UK first

By Jane Kirby, PA Health Editor, published with permission

Katie Tinkler was forced to give up her job as a fitness instructor because of debilitating pain and fatigue caused by severe lupus.

The 50-year-old from Guildford in Surrey, who is married to Simon and has three children, Isabelle, 24, Evie, 20, and Zac, 18, has now been offered the chance of remission through CAR T-cell therapy on the NHS.

The therapy works by genetically modifying the body’s own immune system to recognise and attack problem cells, in this case those that are driving lupus inflammation.

“I was diagnosed with lupus when I was 20,” she told the PA news agency. “I started to get extreme joint pain and, in the first few years, that was my main symptom – like excruciating.

“It was very painful. My hands were so painful I couldn’t hold the steering wheel.”

Next came extreme fatigue and continuing joint pain, followed by antiphospholipid syndrome, which causes blood clots and other health problems, as well as focal myositis (inflammation of skeletal muscle) and kidney disease.

Mrs Tinkler’s main drug regime for lupus has been steroids but recently she has needed more immunosuppressants and other drugs.

“My general health and wellbeing and immune system have been going downhill,” she said, and she has spent three of the last 18 months in hospital.

Despite all this, Mrs Tinkler, who says she has a wardrobe full of sparkly shoes and clothes, is determined to remain positive.

“The way I deal with it is I just get on with it,” she said. “It’s just been the cards that I’ve been dealt with in life.

“I’ve made the best of sometimes a really bad deck of cards and a really awful time, but the way I cope with it is just to get on with it and do the best I can with a situation that I find myself in…

“When I first got diagnosed, I struggled with the diagnosis, and I thought, ‘why me? It’s not fair’.

“And I did struggle. But after a few years, I realised I don’t know why me and it isn’t fair, but it’s sink or swim, and I just find that it’s much easier for me to stay positive, keep going, even if your feet hurt, even if your hands are swollen, even if you find things difficult or you have to cancel doing things, just keep going. Wear a bit of sparkle.”

Mrs Tinkler received her CAR T-cell therapy at University College London Hospitals NHS Foundation Trust (UCLH) on Wednesday this week.

“I am beyond excited,” she said.

“Up until now, there’s never been anything for lupus that is a possible cure.

“When the professor phoned me back in April and said ‘we’re bringing a trial here, would you be interested?’ oh my gosh, I jumped at it.

“I feel that my body’s getting tired, I’ve had this for 30 years, it’s being attacked from inside 24/7, the whole time for 30 years.

“My body’s struggling with it all now, and it’s definitely got worse over the last decade … So I just feel any opportunity that I can have is great.

“If this works, it’s life-changing. And so, gosh, I jumped at it.

“The dream is to be lupus-free – that would be phenomenal.”

Mrs Tinkler believes the clinical trial could bring hope to people who suffer with a range of conditions that have a huge impact on their lives.

“There’s so many autoimmune diseases out there, and there’s 70,000 lupus patients in the UK, so I hope that the results from this trial come out and it gives people the hope that everybody who has an autoimmune disease will be able to have an end point,” she said.

“Up until now, there’s been no cure and no hope of anything, just immunosuppression, which has its own issues.

“So I hope that this trial gives everybody hope with autoimmune disease, that something’s coming their way that will make a massive difference in their lives.”