A teenage girl is recovering from leukemia after becoming the first patient in the world to receive a pioneering cell-editing treatment.
Thirteen-year-old Alyssa, from Leicester, was diagnosed with T-cell acute lymphoblastic leukaemia, which could not be cured by chemotherapy or a bone marrow transplant.
With no options left, doctors at Great Ormond Street Hospital in London attempted a breakthrough experimental therapy in which donated immune T cells were genetically engineered to target her cancer.
The technique, known as base-editing, is the first time a cancer treatment has altered the basic building blocks of DNA.
Experts have changed the genetic code of immune cells to allow them to hunt down and kill cancerous T cells in peace.
After just 28 days, Alyssa was in remission and after a second bone marrow transplant to restore her immune system the leukemia is now undetectable. She is recovering at home and hopes 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 connect cutting-edge technologies in the laboratory with real results in the hospital for patients.
“It is our most sophisticated cell engineering to date and paves the way for other new treatments and ultimately a better future for sick children.”
To create the cells, the healthy donor T cells had to be engineered in four steps. First, the receptors had to be removed from the donated cells to avoid rejection.
Next, a “flag” known as CD7 that identifies them as T cells was removed so that the engineered cells didn’t end up destroying each other.
In the third stage, a second ‘flag’, called CD52, was cut away to make the modified cells invisible to drugs administered to the patient during the treatment process.
Finally, a receptor has been added that allows cells to recognize leukemia 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 base in the gene for CD7 from a cytosine to a thymine creates the equivalent of a genetic point and prevents the immune system from attacking T cells.
Alyssa was diagnosed with T-cell leukemia in May 2021, after a long bout of what the family thought were colds, viruses and general tiredness.
Despite months of treatment in hospitals in Leicester and Sheffield, doctors have been unable to get the cancer under control and in remission.
Kiona, Alyssa’s mother, said: ‘To be honest we are over the moon, it’s great to be home.
“The doctors said the first six months are the most important and we don’t want to get too dismissive, but we kept thinking, ‘If they can get rid of it, just once, he’ll be fine.’ And perhaps we will be right.
“I hope this can show that the research works and that they can offer it to more children – all of this must have gone to something. It seems so nonsensical.
“Alyssa wants to go back to school and it could soon come true.”
Clinical trial in progress
A clinical trial for this treatment is currently open and aims to recruit up to 10 T-cell leukemia patients who have exhausted all conventional treatment options.
If proven to be successful, GOSH’s bone marrow transplant and CAR-T cell therapy teams hope it could be offered to children earlier when they are less sick.
Dr Robert Chiesa, Consultant for Bone Marrow Transplantation and CAR-T Cell Therapy at GOSH, said: ‘This is quite remarkable, although still a preliminary finding, which needs to be monitored and confirmed over the coming months.
“The entire team here at GOSH are extremely happy for Alyssa and her family and it has been a privilege to work with them over the last few months. “
The findings were presented this weekend at the American Society of Hematology’s annual meeting in New Orleans, USA.