Further hope for base-edited T-cell therapy to treat resistant leukaemia

Three young patients with relapsed T-cell leukemia have now been treated with base-edited T-cells, as part of a 'bench-to-bedside' collaboration between UCL and Great Ormond Street Hospital for Children (GOSH).

The data from the NHS clinical trial, shows how donor's CAR T cells were engineered using cutting edge gene editing technology to change single letters of their DNA code so they could fight leukemia.

The experience of using the cells in three patients is shared and includes 13-year-old Alyssa from Leicester, who last year was the first person in the world to be treated on the trial for T-cell acute lymphoblastic leukemia (T-ALL)*. This is a cancer of white blood cells and is usually treated with chemotherapy, but if it comes back, can be hard to clear.

Within four weeks of receiving the cells, Alyssa’s leukemia was undetectable and she went on to have a successful bone marrow transplant and is still well and at home almost a year later.

A second teenager cleared their leukemia within a similar time period and is now recovering at home after their transplant. Sadly, while a third child responded to the CAR T cell therapy, their course was complicated by serious infections and their family agreed with the clinical team to move to palliative care.

To generate banks of ‘universal’ anti-T-cell CAR T-cells for the study, the researchers used healthy donor T-cells, arranged by the Anthony Nolan registry. They then made changes to the cells using ‘base editing’, which works by chemically converting single nucleotide bases (letters of the DNA code) which carry instructions for a specific protein, in order to prevent them being produced.

Reference :Base-edited CAR T Cells for relapsed T-cell acute lymphoblastic leukemia ,New England Journal of Medicine