Universal base-edited CAR7 T cells in acute lymphoblastic leukemia

A new phase 1 trial recently published on The New England Journal of Medicine shows that universal base-edited CAR7 T cells could induce remission in patients with relapsed or refractory acute lymphoblastic leukemia, thus allowing a successful allogeneic hematopoietic stem-cell translplantation.

This first-in-class phase 1 trial involved 9 children under 16 and 2 adults (in a compassionate-use arrangement) with relapsed or refractory acute lymphoblastic leukemia; after lymphodepletion, they received base-edited anti-CD7 CAR (BE-CAR7) T cells, produced by CRISPR C to T base editing on donor T cells. These BE-CAR7 T cells don’t require matching to recipients and results showed that they are safe and can be detected in the blood of all the patients. At day 28, nine patients (82%) had deep remission that allowed them to proceed to stem-cell transplantation, that eliminated remaining BE-CAR7 T cells and supported donor-derived, multilineage reconstitution. Overall, 7 of the 11 patients (64%) who received the investigational therapy were in ongoing remission at 3 to 36 months after transplantation. Viral reactivations were frequent, and 3 patients had clinically significant virus-related complications after transplantation; leukemia with loss of CD7 expression was documented in 2 patients. As lead researcher Waseem Qasim from University College London said, «We previously showed promising results using precision genome editing for children with aggressive blood cancer and this larger number of patients confirms the impact of this type of treatment. We’ve shown that universal or ‘off the shelf’ base-edited CAR T cells can seek and destroy very resistant cases of CD7+ leukemia. Limitations of this approach included CD7 antigen loss and risks of viral-related complications».