Allogeneic double-negative T-cell therapy for acute myeloid leukemia.

CD3+CD4-CD8- double-negative T cells (DNTs) represent a unique subset of T lymphocytes with potent cytotoxicity against acute myeloid leukemia (AML). Importantly, allogeneic DNTs do not induce graft-versus-host disease and have demonstrated characteristics suitable for off-the-shelf cellular therapy with promising efficacy in early-stage clinical trials. DNT therapy can synergize with conventional AML treatments and can be transduced with chimeric antigen receptors (CARs). Notably, persistent CAR+ T cells in patients, who achieved long-term remission, predominantly have a DNT phenotype. The unique and versatile therapeutic properties of allogeneic DNTs position them as a strong candidate among adoptive cellular therapies for AML.