RARE Daily

UK Researchers Report First Results from Human Application of Base-Edited T Cell Therapy to Treat Leukemia

June 15, 2023

Rare Daily Staff

Researchers at University College London and Great Ormond Street Hospital for Children reported interim results on the first three pediatric patients with relapsed T-cell leukemia treated with the first human application of base-edited T cells.

Though the results are being hailed as showing the potential for the approach, one of the three children in the study, though responsive to the CAR T cell therapy, suffered complications from a serious infection and the family agreed with the clinical team to move the child to palliative care. The researchers said the interim results of the phase 1 study support further investigation of base-edited T cells for patients with relapsed leukemia and indicate anticipated risks of immunotherapy-related complications.

The interim results from the study were published in the New England Journal of Medicine. The trial for the treatment is still open and will recruit up to 10 patients from the United Kingdom’s National Health Service with T-cell leukemia who have exhausted all conventional treatment options and been referred by NHS children’s leukemia specialists. Patients in the study are treated in the Bone Marrow Transplant Department at Great Ormond Street Hospital for Children (GOSH).

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 in 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.

The study used base editing to generate universal, off-the-shelf chimeric antigen receptor (CAR) T cells. The researchers began with healthy volunteer donor T cells and used a lentivirus vector to alter the cells to make the cells specific to CD7, a protein expressed in T-cell acute lymphoblastic leukemia (ALL). They then used base editing to inactivate three genes encoding CD52 and CD7 receptors and the beta chain of the alpha beta T-cell receptor to evade destruction of these cells by treatments, CAR7 T-cell fratricide and graft-versus-host disease.

Within four weeks of receiving the cells, the first patient’s leukemia was undetectable and she then had a successful bone marrow transplant. She is still well and at home almost a year later. The second patient cleared their leukemia within a similar time period and is now recovering at home after their transplant.

“It’s nice to be able to see the fruits of a long period of work coming together from multiple teams and being brought into play for new treatments,” said Waseem Qasim, professor of Cell and Gene Therapy at UCL, who led the team that designed and developed the therapy. “It’s still early, and we need more follow up and to treat more patients to know how it might impact treatments long term.”

If shown to be widely successful, the researchers hope it can be offered to more children and earlier in their treatment journey, as well as adults in the future. The researchers also believe the base editing technique could be used for multiple other conditions, where changes in single letters of DNA cause illness, such as sickle cell disease.


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