GOSH researchers develop breakthrough treatment for previously incurable leukaemia

The patient, 13-year-old Alyssa from Leicester, was diagnosed with T-cell acute lymphoblastic leukaemia (T-ALL) in 2021.

She was treated with all the current conventional therapies, including chemotherapy and a bone marrow transplant (BMT).

However, the disease came back.

Without this new, experimental treatment, delivered as part of a clinical trial, the only remaining option for Alyssa would have been palliative care.

Thanks to the incredible researchers at GOSH and University College London, Alyssa was able to receive ‘universal’ CAR T-cells that had been pre-manufactured from a healthy volunteer donor.

These cells had been gene-edited using new base-editing technology and fitted with a Chimeric Antigen Receptor (CAR) that allow them to recognise, hunt down and kill cancerous T-cells without attacking each other.

(Base-editing works by chemically converting the molecules that make up DNA, called nucleotide bases. This works differently to other treatments like CRISPR/Cas9 that use molecular 'scissors' to cut and edit DNA. The new base editing approach acts without causing breaks in the DNA, allowing more edits to be made. Watch the video below to learn more.)

Just 28 days after receiving the cells, Alyssa was in remission and went on to receive a second bone marrow transplant to restore her immune system.

Alyssa is the first patient in the world reported to have received a base-edited cell therapy. One reason she wanted to take part in the experimental treatment was to help other patients like herself.

“Once I do it, people will know what they need to do, one way or another, so doing this will help people – of course I’m going to do it,” she said ahead of the treatment.

Now, six-months post-BMT, she is currently at home recovering from her treatment. “We’re on a strange cloud nine to be honest – it’s amazing," Alyssa’s mum, Kiona, says.

The family are feeling positive that the leukaemia is now undetectable but know she will need to be monitored closely for some time.

Dr Robert Chiesa, Consultant in Bone Marrow Transplant and CAR T-cell therapy at GOSH, says:

"Only after she received her CD7 CAR-T cell therapy and a second bone marrow transplant in GOSH she has become leukaemia free. This is quite remarkable, although it is still a preliminary result, which needs to be monitored and confirmed over the next few months.

"The entire team here at GOSH are extremely happy for Alyssa and her family and it’s been a privilege to work with them over the past few months. We have been very impressed by how brave she is and nothing makes me happier than seeing her outside the hospital, going back to a more normal type of life."

Trials like this wouldn’t be possible without many different teams at GOSH. These include the hospital's Bone Marrow Transplant team, CAR T-cell therapy experts, haematology service, research nurses, allied health professionals, Play team and so many more.

The ‘universal’ CAR T-cells were manufactured as part of a long-standing research programme led by Professor Waseem Qasim at UCL Great Ormond Street Institute of Child Health. Professor Qasim is also an Honorary Consultant at GOSH and his team is based at the Zayed Centre for Research into Rare Disease in Children.

Thanks in part to early funding from GOSH Charity, Professor Qasim has been a pioneer in developing new CAR T-cell treatments using innovative gene editing techniques.

The knowledge he has built up over time has helped to pave the way for this new base-editing technique.

“This is a great demonstration of how, with expert teams and infrastructure, we can link cutting edge technologies in the lab with real results in the hospital for patients,” Professor Qasim says of the breakthrough.

“It’s our most sophisticated cell engineering so far and paves the way for other new treatments and ultimately better futures for sick children.

“We have a unique and special environment here at GOSH that allows us to rapidly scale up new technologies and we’re looking forward to continuing our research and bringing it to the patients who need it most.”

Want to know more? Below is a roundup of articles and social media posts offering more information on this exciting research news from GOSH.

• BBC News | Base editing: Revolutionary therapy clears girl's incurable cancer
• GOSH News item | GOSH patient receives world-first treatment for her 'incurable' T-cell leukaemia
• American society of haematology | Researchers presented the data for the first time at the American Society of Haematology annual meeting in New Orleans, USA, over the weekend.