Adoptive NK cell therapy in AML: progress and challenges.

Adoptive cell therapy (ACT) using natural killer (NK) cells has emerged as a promising therapeutic strategy for acute myeloid leukemia (AML), addressing challenges such as chemotherapy resistance and high relapse rates. Over the years, clinical trials and studies have explored various sources of NK cells, including ex vivo expanded NK cell lines, CAR-NK cells, peripheral blood-derived NK cells, and umbilical cord blood-derived NK cells. These therapies have demonstrated varying degrees of therapeutic efficacy, ranging from transient anti-leukemia activity to sustained remission in select patient groups. Toxicity profiles have generally shown favorable safety outcomes, with minimal incidence of severe adverse effects such as cytokine release syndrome (CRS) or graft-versus-host disease (GVHD). However, persistent challenges remain, including limited NK cell persistence, relapse, and heterogeneity in patient responses. This review provides a comprehensive analysis of clinical outcomes and toxicity profiles provided from clinical trials, clinical studies and case reports conducted in the last 15 years to judge on the efficacy, safety and applicability of using NK cells for ACT of AML. Our review highlights the significant potential of NK cell-based therapies for AML, while addressing the technical and biological challenges that must be overcome to enhance their efficacy and safety.