The New England Journal of MedicineBase-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia

Base-Editing Technique Overcomes CAR T-Cell Fratricide in T-cell Cancers

A new study has demonstrated the potential of base editing in CAR T-cell therapy for treating T-cell cancers. The study, which involved pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia (ALL), used CRISPR-guided cytidine deamination to prevent CAR T-cell fratricide and graft-versus-host disease (GVHD). The results indicate a promising avenue for overcoming the challenges associated with CAR T-cell therapy in T-cell malignancies.

HCN Medical Memo
For physicians involved in the treatment of T-cell malignancies, this study offers a promising approach to overcoming the limitations of current CAR T-cell therapies. The use of base editing to prevent fratricide and GVHD could significantly broaden the applicability of CAR T-cell therapy in T-cell cancers. However, it’s crucial to note that the study is still in its early phase, and further research is needed to confirm these findings and assess long-term safety.

Key Points:

• The study used CRISPR-guided cytidine deamination to edit T-cell antigens and prevent CAR T-cell fratricide and GVHD.
• The phase I study involved pediatric patients with relapsed or refractory T-cell ALL.
• The base-edited CAR7 (BE-CAR7) T cells were generated from healthy donor T cells and used in a feasibility and safety study.
• The first three study participants showed promising results, with two achieving deep remission.
• Physicians and researchers have expressed cautious optimism, noting that the base-editing technique could revolutionize CAR T-cell therapy for T-cell cancers.

Approximately 3,000 new cases of acute lymphoblastic leukemia (ALL) are diagnosed in children and adolescents in the United States each year, making it the most common form of childhood cancer.

Additional Points:

• Patients received lymphodepletion with fludarabine, cyclophosphamide, and alemtuzumab before BE-CAR7 T-cell infusion.
• The study is being conducted with the approval of the United Kingdom Health Research Authority and has ethical approval from the West London Ethics Committee.
• Some patients experienced side effects like cytokine release syndrome and viral reactivations, which were managed with established protocols.

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