A 13-year-old British girl who was diagnosed with T-cell acute lymphoblastic leukemia in 2021 and who had not responded well to standard treatments with chemotherapy and bone marrow transplantation has become the first patient to have beaten the disease. resistant after participating in a clinical trial in which he was given therapy with ‘universal’ CAR T cells that had been pre-manufactured from those obtained from a healthy donor.
Now, leukemia is undetectable in Alyssa, the young patient whose cancer had become incurable after exhausting the treatment options available to that point. The girl was the first patient to be enrolled in the TvT clinical trial and in May 2022 she was admitted to the Bone Marrow Transplantation (BMT) Unit at the Great Ormond Street Hospital (GOSH)to receive ‘universal’ CAR T cells that had been edited using a novel base-editing technology, designed and developed by a group of UCL scientists, led by Professor Waseem Qasim (UCL Great Ormond Street Institute of Children’s Health ), who is also an honorary consultant at GOSH.
She was then put in a chimeric antigen receptor (CAR) to allow them to hunt down and kill cancer T cells without attacking each other, and within 28 days Alyssa was in remission and received a second bone marrow transplant to restore her immune system. Six months have elapsed since the BMT, and the patient is recovering at home with her family and continues her post-BMT follow-up at GOSH. If she had not been given this experimental treatment, Alyssa’s only option was hospice care.
The girl only became free of leukemia “after receiving her CD7 CAR-T cell therapy and a second bone marrow transplant”
The encouraging results of this experimental therapy against leukemia have just been presented for the first time at the annual meeting of the American Society of Hematology in New Orleans (United States). Waseem Qasim, Professor of Cell and Gene Therapy at UCL GOS ICH, and Consultant Immunologist at GOSH, explained: “We designed and developed the treatment from the laboratory to the clinic and are now testing it in children across the UK, in a unique approach from bank to parent”.
“Alyssa’s story 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 is our most sophisticated cell engineering yet and paves the way for other new treatments and ultimately better futures for sick children.” “We have a special and unique environment here at GOSH and UCL that allows us to quickly scale up new technologies and we look forward to continuing our research and bringing it to the patients who need it most.”
‘Universal’ T cells to cure children with leukemia
The clinical trial of this treatment continues with the aim of recruiting up to 10 patients with T-cell leukemia in whom none of the conventional treatments have worked. If proven effective, the CAR T-cell therapy and bone marrow transplantation teams at GOSH hope that it can be offered to children in the early stages of the disease, and that further applications of this treatment will also be found for other types of leukemia by 2023. NHS specialists fighting hard-to-treat childhood leukemia across the country discuss and refer patients to such trials.
Dr. Robert Chiesa, consultant in bone marrow transplantation and CAR T cell therapy at GOSH, has stated that “since Alyssa fell ill with leukemia in May of last year, she has never achieved a complete remission. Not with chemotherapy, and not after her first bone marrow transplant. Only after receiving her CD7 CAR-T cell therapy and a second bone marrow transplant at GOSH was she free of leukemia.” “This is quite remarkable, although it is still a preliminary result, which must be monitored and confirmed in the coming months.”
T cells designed to recognize and attack cancer cells also end up killing each other during the laboratory manufacturing process, so this study required numerous additional DNA changes to generate anti-T cell CAR T cell banks. ‘universals’. The result is edited CAR T cells that can be given to the patient to rapidly locate and kill T cells in the body, including leukemic T cells. If the treatment is successful, the patient receives a bone marrow transplant to restore his depleted immune system.
Previous treatments have been based on techniques called TALENS or CRISPR/Cas9 to generate changes in genes through cuts made with molecular ‘scissors’. The base-editing method does not cause breaks in the DNA, allowing for further editing, with less risk of unwanted effects on the chromosomes. The technique is also being investigated to try to correct harmful changes in the DNA code for various hereditary conditions.
Dr Louise Jones, Head of Translation for the Medical Research Council, which funded the project through its Development Track Funding Scheme, said: “We are delighted to hear of the promising results of this treatment and hope that has given Alyssa and her family. Advanced therapies – gene, tissue or cell-based drugs – have the potential to transform the lives of people with difficult-to-treat diseases and remain a priority for the MRC. If replicated, this ‘off the shelf’ universal cell therapy will mark a huge step forward in such therapies that will deliver life-changing benefits to more patients.”
.
