Creation of a functional CD33 | CD16b Tmod construct required solution of two technical problems: (i) selection of a blocker antigen that is compatible with blocker function and the inverse of an AML TAA (i.e., with expression that is low in AML and high in normal blood cells); and (ii) identification of an scFv that can distinguish CD16b from its very close paralog, CD16a, which is expressed in a subset of AML malignancies and thus could limit efficacy. Here, CD33 is linked to acute myeloid leukemia.