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**ULBP2-aCD19-aCD33** is a preclinical recombinant trispecific immunoligand, or triplebody, designed to redirect natural killer cells against leukemic cells expressing CD19, CD33, or both antigens. It combines the natural NKG2D ligand UL16-binding protein 2 with anti-CD19 and anti-CD33 single-chain variable fragments. By binding NKG2D on natural killer cells while simultaneously engaging CD19 and CD33 on malignant cells, it promotes natural killer cell-mediated cytotoxicity and may mitigate single-antigen escape. Published work demonstrated activity against CD19/CD33-positive leukemia cell lines and primary leukemic blasts, including biphenotypic B/myeloid leukemia specimens, but also identified potential on-target effects against CD33-expressing natural killer cells and normal CD19-positive B cells.
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