Universal Base-Edited CAR7 T Cells for T-Cell Acute Lymphoblastic Leukemia

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.

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.

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.

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.)

NOTES

This article was published on December 8, 2025, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Supported by grants from the Medical Research Council (MR/W014726/1, to Robert Chiesa, Roland Preece, and Waseem Qasim), the Wellcome Trust (to Christos Georgiadis, Annie Etuk, and Waseem Qasim), the National Institute for Health Research (to Waseem Qasim and the Great Ormond Street Hospital Biomedical Research Centre), and the Great Ormond Street Hospital Children’s Charity.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank the patients and their families for participating in this study, as well as the volunteer donors arranged by the Anthony Nolan stem-cell charity.

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