Base-Edited Donor CAR-T Yields 82% Transplant-Eligible Remission in Early T-Cell Leukemia Trial

Overview

• Phase 1 results from UCL and Great Ormond Street Hospital were published in the New England Journal of Medicine and presented at ASH, reporting 82% remission sufficient for transplant and 64% disease-free with follow-up up to three years.
• The first 11 patients treated at Great Ormond Street and King’s College Hospital included children and adults who had failed chemotherapy and prior transplants.
• Researchers used base editing to remove receptors that could trigger graft-versus-host effects, delete CD7 to prevent self-recognition, delete CD52 to evade an antibody, and add a CAR to target T cells.
• The protocol ablates the patient’s immune system, infuses the edited cells to clear malignant and normal T cells within weeks, then proceeds to a bone marrow transplant to rebuild immunity.
• Major risks center on infections during immune ablation, with reported cytopenias, cytokine release syndrome and rashes, and two relapses occurred via CD7 loss; the first treated patient remains cancer-free on annual follow-up.