Highly-avid healthy donor CD8+ T cell clones killed CBFB-MYH11+ HLA-B*40:01+ AML cell lines and primary human AML samples in vitro. CBFB-MYH11–specific T cells also controlled CBFB-MYH11+ HLA-B*40:01+ AML in vivo in a patient-derived murine xenograft model. Transduction of high-avidity CBFB-MYH11 epitope–specific T cell receptor into CD8+ T cells conferred antileukemic potential. The gene discussed is CBFB; the disease is acute myeloid leukemia.