Phase 1 study of base-edited CAR7 T cells for relapsed T-cell acute lymphoblastic leukemia

Cytidine deamination that is guided by CRISPR can mediate highly precise conversion of cytosine to thymine without generating breaks in DNA. Thus, genes can be base-edited and rendered inactive without inducing translocations and other chromosomal aberrations. Researchers at two centers in London (UK) used CAR T cells with specificity for CD7 (a protein that is expressed in T-cell ALL) and base-edited these cells to evade lymphodepleting serotherapy, CAR7 T-cell fratricide, and graft-versus-host disease. These base-edited cells (BE-CAR7) showed potent activity in patients with pediatric relapsed T-cell ALL. Serious adverse events included cytokine release syndrome, multilineage cytopenia, and opportunistic infections. The authors conclude that the interim results of this phase 1 study support further investigation of BE-CAR7 for patients with relapsed leukemia, and indicate the anticipated risks of immunotherapy-related complications.