A teenage girl is recovering from leukaemia after becoming the first patient in the world to receive a pioneering cell-editing treatment.
The 13-year-old, named Alyssa, from Leicester, was diagnosed with T-cell acute lymphoblastic leukaemia, which could not be treated with chemotherapy or a bone marrow transplant.
With no options left, doctors at Great Ormond Street Hospital in London, attempted a groundbreaking experimental therapy in which donated immune T-cells were genetically edited to target her cancer.
The technique, known as base-editing, is the first time a cancer treatment has altered the fundamental building blocks of DNA.
Experts changed the genetic code of immune cells to allow them to hunt down and kill cancerous T-cells while leaving themselves alone.
After just 28 days, Alyssa was in remission and after a second bone marrow transplant to restore her immune system the leukaemia is now undetectable. She is recovering at home and hoping to go back to school soon.
Professor Waseem Qasim, Professor of Cell and Gene Therapy at UCL GOS ICH and Consultant Immunologist at GOSH said: “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.
“It’s our most sophisticated cell engineering so far and paves the way for other new treatments and ultimately better futures for sick children.”
To create the cells, healthy donor T-cells needed to be engineered in four stages. Firstly, receptors needed to be removed from the donated cells to avoid rejection.
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Next, a “flag” known as CD7 that identifies them as T-cells was removed so that the engineered cells did not end up destroying each other.
In the third step, a second “flag”, called CD52, was snipped away to make the edited cells invisible to drugs given to the patient during the treatment process.
Finally, a receptor was added allowing the cells to recognise leukemic T-cells.
These changes were achieved by “base editing” – chemically converting single nucleotide bases or letters of the DNA code, which carry instructions.
For example, changing the nucleotide bases in the gene for CD7 from a cytosine to a thymine creates the equivalent of a genetic full stop, and stops the immune system attacking T-cells.
Alyssa was diagnosed with T-cell leukaemia in May 2021, after a long period of what the family thought were colds, viruses and general tiredness.
Despite months of treatment in hospitals in Leicester and Sheffield medics were unable to get her cancer under control and into remission.
Kiona, Alyssa’s mother said: “We’re on a strange cloud nine to be honest – it’s amazing to be home.
“The doctors have said the first six months are the most important and we don’t want to get too cavalier but we kept thinking ‘If they can just get rid of it, just once, she’ll be ok.’ And maybe we’ll be right.
“Hopefully this can prove the research works and they can offer it to more children – all of this needs to have been for something. It just feels so senseless.
“Alyssa wants to go back to school and that could be a reality soon.”
Clinical trial ongoing
A clinical trial for this treatment is currently open and aims to recruit up to 10 patients with T-cell leukaemia who have exhausted all conventional treatment options.
If shown to be successful, the bone marrow transplant and CAR T-cell therapy teams at GOSH hope it can be offered to children earlier when they are less sick.
Dr Robert Chiesa, consultant in bone marrow transplant and CAR T-cell therapy at GOSH, said: “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. “
The results are being presented this weekend at the American Society of Haematology annual meeting in New Orleans, US.
