From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor prognosis despite advances in treatment strategies. Standard treatment regimens induce remissions in many patients, but relapse occurs in approximately half, highlighting the urgent need for novel therapeutic strategies. Antibody-based therapies have significantly improved the treatment of acute lymphoblastic leukemia (ALL), but progress in AML has been slower, with only gemtuzumab ozogamicin (GO) receiving FDA approval to date. This is largely due to the absence of AML-specific surface antigens and the challenge of distinguishing malignant blasts from normal hematopoietic cells, which raises concerns about on-target/off-leukemia toxicity. Nonetheless, a wide range of antibody constructs, including unconjugated monoclonal antibodies, antibody-drug conjugates, and bispecific T cell engagers (BTCEs), are now under investigation in both preclinical studies and clinical trials, predominantly in the relapsed/refractory (R/R) setting. Encouraging results from early-phase studies suggest that antibody-based approaches could complement or even partially replace traditional cytotoxic regimens in selected patient groups. In this review, we summarize the spectrum of antigenic targets explored for AML immunotherapy, critically assess clinical outcomes achieved so far, and discuss current efforts to improve efficacy, durability, and safety. We also highlight emerging strategies aimed at overcoming antigen heterogeneity and resistance, thereby advancing antibody-based therapies toward broader clinical application in AML.