University College London (UCL) and Great Ormond Street Hospital (GOSH) have reported promising findings from a gene therapy that has been tested in patients with an aggressive blood cancer

BE-CAR7 is a donor-derived CAR T-cell product created using base-editing technology. The approach involves making precise changes to DNA without introducing double-strand breaks, allowing researchers to modify healthy donor T cells so they can target malignant T cells while avoiding self-destruction and immune rejection. The aim is to produce an “off-the-shelf” therapy that can be administered without the delays associated with manufacturing patient-specific CAR T cells.

The first patient treated was a 13-year-old girl called Alyssa Tapley, who had exhausted all available treatment options for refractory T-cell acute lymphoblastic leukaemia (T-ALL). She received the therapy in 2022 as part of an early clinical trial conducted at GOSH, becoming the first person in the world to receive a base-edited CAR T-cell therapy. Following treatment, she achieved remission and was able to proceed to a stem cell transplant.

Since that initial case, a further eight children and two adults with advanced T-ALL have been treated in the ongoing study. Results have now been published in The New England Journal of Medicine.

Waseem Qasim, a Professor of Cell and Gene Therapy at UCL who led the research, said: “A few years ago this would have been science fiction. Now we can take white blood cells from a healthy donor and change a single letter of DNA code in those cells and given them back to patients to try to tackle this hard-to-treat leukaemia. We designed and developed the treatment from lab to clinic and are now trialling it on children from across the UK – in a unique bench-to-bedside approach.”

Across the treated cohort, 82 per cent of patients achieved deep remission following BE-CAR7 treatment, allowing them to move on to stem cell transplantation without detectable disease. At the time of reporting, 64 per cent of patients remained disease-free at follow-up, with the earliest treated individuals approaching three years without evidence of cancer and no longer requiring active therapy.

Tapley says: “I am really grateful for all the opportunities the gene therapy treatment has given me. I feel like I have been able to help everyone else who went on the clinical trial after me. I’ve now been able to do some of the things I thought earlier in my life it would be impossible for me to do. I really did think I was going to die and that I wouldn’t be able to grow up and do everything that every child deserves to be able to do.”

UCL says that additional funding has been secured to support treatment of further patients as part of an expanded trial cohort, with ongoing work focused on evaluating safety, durability of response and broader applicability of the approach.