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CD123-FLT3 HLE dBiTE is a half-life extended (HLE) dual-targeting bispecific T-cell engager (dBiTE) developed by Amgen for the treatment of acute myeloid leukemia (AML). The molecule is designed to simultaneously target two tumor-associated antigens, CD123 (interleukin-3 receptor alpha) and FLT3 (FMS-like tyrosine kinase 3), while engaging CD3 on T cells to induce redirected lysis of leukemic cells. This dual-targeting approach aims to reduce the frequency of relapse caused by the loss of a single antigen. Preclinical evaluations in vitro and in mouse xenograft models demonstrated potent cytotoxicity against both single-positive and double-positive target cells. However, studies in non-human primates revealed tolerability challenges, including cytokine release and potential off-target effects on endothelial cells, where CD123 expression can be upregulated under inflammatory conditions.
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