2025-12-08 ユニバーシティ・カレッジ・ロンドン(UCL)
<関連情報>
- https://www.ucl.ac.uk/news/2025/dec/world-first-base-edited-gene-therapy-helps-patients-fight-previously-incurable-blood-cancer
- https://www.nejm.org/doi/full/10.1056/NEJMoa2505478
T細胞急性リンパ芽球性白血病に対するユニバーサル塩基編集CAR7 T細胞 Universal Base-Edited CAR7 T Cells for T-Cell Acute Lymphoblastic Leukemia
Robert Chiesa, M.D., Christos Georgiadis, Ph.D., Hebatalla Rashed, M.B., B.Ch., Roland Preece, Ph.D., Prudence Hardefeldt, M.D., Jan Chu, M.Sc., Jemma Selvage, B.Sc., +9 , for the Base-Edited CAR T Group
New England Journal of Medicine Published: December 8, 2025
DOI: 10.1056/NEJMoa2505478
Abstract
Background
CD7 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory T-cell acute lymphoblastic leukemia (ALL). Supportive results of first-in-human studies of base-edited anti-CD7 CAR (BE-CAR7) T cells with triple C→T deamination-mediated knockouts of TCRαβ, CD52, and CD7 have been reported previously.
Methods
In a phase 1 study, we administered BE-CAR7 T cells to children (≤16 years of age) with relapsed or refractory T-cell ALL after they had undergone lymphodepletion with fludarabine, cyclophosphamide, and alemtuzumab. Adults with compassionate-use access arrangements were also eligible. Patients who had remission by day 28 after the BE-CAR7 T-cell infusion proceeded to allogeneic hematopoietic stem-cell transplantation. The primary outcome was safety. Secondary outcomes included duration of remission, disease-free survival, and overall survival.
Results
BE-CAR7 T cells were administered to 9 children, as well as to 2 adults who were treated under compassionate-use access arrangements. Lymphodepletion and BE-CAR7 infusions did not lead to unacceptable adverse events, and circulating CAR7 T cells were detected in all the patients. Complications included cytokine release syndrome of grades 1 through 4, transient rashes, multilineage cytopenia, and opportunistic infections. All the patients had complete morphologic remission with incomplete count recovery at day 28. Nine patients (82%) had deep remission (according to flow cytometry or polymerase-chain-reaction assay) that allowed them to proceed to stem-cell transplantation, and 2 patients with quantifiable minimal residual disease in bone marrow received palliative care. Transplantation eliminated remaining BE-CAR7 T cells and supported donor-derived, multilineage reconstitution. Viral reactivations were frequent, and 3 patients had clinically significant virus-related complications after transplantation. Overall, 7 of the 11 patients (64%) who received the investigational therapy were in ongoing remission at 3 to 36 months after transplantation, and leukemia with loss of CD7 expression was documented in 2 patients.
Conclusions
Universal BE-CAR7 T cells induced leukemic remission in patients with relapsed or refractory T-cell ALL, thus allowing successful allogeneic hematopoietic stem-cell transplantation in most of the patients. (Funded by the Medical Research Council and others; ISRCTN Registry number, ISRCTN15323014.)
