Non-gene-edited, CD19-targeted, allogeneic CAR-T cell therapy for relapsed or refractory B-cell acute lymphoblastic leukemia: an open-label, single-arm phase 1 study.

Autologous chimeric antigen receptor (CAR)-T cell therapy is effective in relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), but its clinical application is restricted by manufacturing failures, high costs, and limited accessibility. Gene-edited allogeneic CAR-T cells offer an off-the-shelf alternative, yet concerns remain regarding genomic instability and graft-versus-host disease (GVHD). We conducted a phase 1 study to assess the safety and efficacy of ThisCAR-T, a non-gene-edited, CD19-directed allogeneic CAR-T cell product, in patients with R/R B-ALL. Eleven patients were treated with escalating doses of ThisCAR-T at 1 × 106, 3 × 106, and 5 × 106 cells/kg. One patient withdrew after infusion. Among the remaining ten patients, eight developed cytokine release syndrome, including seven with grade 1-2 and one with grade 3. Immune effector cell-associated neurotoxicity syndrome occurred in two patients (grade 1 and grade 4, respectively). No GVHD was observed. At day 28, 8 of 9 evaluable patients achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi). At a median follow-up of 31 months, the 1-year progression-free survival and overall survival rates were 30% and 40%, respectively. ThisCAR-T demonstrated a favorable safety and promising antileukemic activity, supporting its potential as a novel therapy for R/R B-ALL.