Patients disease-free after base editing gene therapy for aggressive leukaemia

Eleven people with aggressive T-cell leukaemia have now received a 'base editing' therapy, with seven remaining in remission up to three years after treatment.

Researchers from Great Ormond Street Hospital (GOSH), University College London (UCL), and King's College Hospital, London, have reported new results from an ongoing phase 1 clinical trial of the experimental treatment, known as BE-CAR7. Eleven patients with T-cell acute lymphoblastic leukaemia that did not respond to chemotherapy treatment, or whose cancer had returned after chemotherapy, have now been treated with BE-CAR7. Seven of the 11 patients remain cancer-free between three and 36 months after receiving the therapy.

'Although most children with T-cell leukaemia will respond well to standard treatments, around 20 percent may not. It's these patients who desperately need better options and this research provides hope for a better prognosis for everyone diagnosed with this rare but aggressive form of blood cancer,' said Dr Robert Chiesa, bone marrow transplant consultant at GOSH and first author of the study published in the New England Journal of Medicine.

Scientists at GOSH and UCL developed the therapy by making chimeric antigen receptor T cells (CAR-T cells) capable of recognising and destroying cancer cells. The first patient, 13-year-old Alyssa Tapley, was treated in 2022 (see BioNews 1172) and remains disease-free.

'I am really grateful for all the opportunities the gene therapy treatment has given me,' said Alyssa. '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.'

The trial continued with a small cohort of three children. Two of the three treated children achieved remission within 28 days of therapy. The third patient initially showed a treatment response but subsequently developed a fatal infection, highlighting the potential risks associated with this immunotherapy (see BioNews 1195).

BE-CAR7 uses base editing, a form of CRISPR genome editing that can change single DNA letters without cutting the DNA strand. Traditionally, CAR-T cells administered to cancer patients are generated using the patient's own T cells, which are often exhausted and dysfunctional due to disease burden. Contrastingly, BE-CAR7 is engineered from healthy donor T cells that do not need to be precisely genetically matched to patients, allowing the creation of an 'off-the-shelf', universal treatment.

Among the nine children treated at GOSH and two adults treated at King's, nine achieved deep remission, allowing them to proceed to stem-cell transplant with no detectable disease. Side effects included episodes of low blood counts and viral infections after transplant, but clinicians report that most complications were manageable within routine care.

Commenting on the outlook of the research, Dr Tania Dexter, senior medical officer at UK stem cell charity Anthony Nolan, said: 'As with any novel cellular therapy, this phase 1 trial is just an initial indication of the effectiveness and safety of the treatment, and more work must be done to determine its wider clinical application. Yet the results are encouraging and demonstrate the recent leaps in technology that are allowing us to take on even greater challenges in the treatment of blood cancers and blood disorders.'

The trial is currently still accepting patients who are eligible to undergo the therapy under the NHS.