First Patient Receives Base-Edited CAR T-Cell Therapy to Treat Resistant T-Cell Leukemia

A teenager in the United Kingdom is in complete remission from resistant T-cell acute lymphoblastic leukemia (T-ALL) following treatment with a novel base-edited chimeric antigen receptor (CAR) T cell therapy at Great Ormond Street Hospital (GOSH) in London.

The 13-year-old patient was diagnosed with T-ALL in 2021 and originally treated with conventional therapies, including chemotherapy and a bone marrow transplant. After her cancer returned, she was the first patient enrolled in a clinical trial to receive base-edited CAR T cells – a world-first treatment.

According to a hospital statement, treating T-ALL with traditional CAR T-cell therapy can be difficult because the T cells designed to recognize and attack cancerous T cells often end up killing each other before they can be given as a treatment.

To address this, a team of investigators from GOSH and University College London (UCL) used a genome editing technique called base-editing to develop CAR T cells that can attack cancerous T cells without killing each other.

Base editing works by chemically converting single letters of the DNA code to change T cells. According to UCL, base editing differs from other gene editing techniques because it acts without causing breaks in the DNA, therefore allowing more edits with less risk of unwanted effects on chromosomes.

To develop the base-edited T cells, the team first modified healthy donor T cells so that they would not be attacked by her immune system. Investigators then removed the CD7 T-cell marker on the cells so they would not attack each other before being used as treatment. Next, investigators removed CD52, which made the modified cells invisible to other cancer treatments. Finally, the investigators added a chimeric antigen receptor, which recognizes the CD7 T-cell receptor on leukemic T-cells.

If the treatment is successful, patients go on to receive a bone marrow transplant to restore their depleted immune systems. This first patient received her second bone marrow transplant 28 days after her treatment; she is recovering at home and continues to be monitored.

The clinical trial for this treatment is currently open and aims to recruit up to 10 patients with T-cell leukemia who have exhausted all conventional treatment options. If shown to be widely successful, the bone marrow transplant and CAR T-cell therapy teams at GOSH hope it can be offered to pediatric patients earlier in their course of treatment.