Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells

TLDR

Autologous CAR19 T‑cell therapy shows marked remissions but is hard to manufacture for infants or heavily pre‑treated patients. The authors produced universal CAR19 T cells by lentiviral transduction of non‑HLA‑matched donor cells and TALEN‑mediated deletion of the TCRα and CD52 loci, then infused a single dose after lymphodepletion and anti‑CD52 serotherapy into two relapsed infants. Both infants achieved molecular remission within 28 days, with UCART19 cells persisting until conditioning for allogeneic stem‑cell transplantation, illustrating the therapeutic promise of gene‑edited CAR T cells.

Abstract

Autologous T cells engineered to express chimeric antigen receptor against the B cell antigen CD19 (CAR19) are achieving marked leukemic remissions in early-phase trials but can be difficult to manufacture, especially in infants or heavily treated patients. We generated universal CAR19 (UCART19) T cells by lentiviral transduction of non-human leukocyte antigen-matched donor cells and simultaneous transcription activator-like effector nuclease (TALEN)-mediated gene editing of T cell receptor α chain and CD52 gene loci. Two infants with relapsed refractory CD19+ B cell acute lymphoblastic leukemia received lymphodepleting chemotherapy and anti-CD52 serotherapy, followed by a single-dose infusion of UCART19 cells. Molecular remissions were achieved within 28 days in both infants, and UCART19 cells persisted until conditioning ahead of successful allogeneic stem cell transplantation. This bridge-to-transplantation strategy demonstrates the therapeutic potential of gene-editing technology.