CAR T and NK cell therapy for acute myeloid leukemia

Adoptive cell therapy has emerged as a powerful approach for treating hematologic malignancies. Among these strategies, chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable clinical efficacy, especially for treating B cell malignancies. Several CAR T cell products have been approved for clinical use. Additionally, CAR-engineered natural killer (CAR NK) cells have recently been developed and have shown promising results in clinical trials for treating B-cell malignancies. However, developing CAR T- or NK-cell therapies for acute myeloid leukemia (AML) has been challenging due to the lack of AML-specific antigens that are not expressed by normal hematopoietic cells. Recently, we developed CAR T- and CAR NK-cell therapies targeting mismatched human leukocyte antigen (HLA)-DRB1 molecules in patients who have undergone allogeneic hematopoietic cell transplantation (allo-HCT). This review summarizes the current status of AML therapy, discusses the challenges of identifying suitable CAR targets, and introduces CAR T- and CAR NK-cell strategies targeting mismatched HLA-DRB1 molecules for treating relapsed AML after allo-HCT.