Targeting CD123 in AML.

An ideal cell surface target for therapy in leukemia would be: tumor-specific (not expressed on normal cells) or at least enriched on tumor cells, necessary for tumor but not for normal cell survival, internalized efficiently (if the surface-targeted agent is conjugated to chemotherapy or a toxin molecule), and recycled rapidly to the cell surface. While a single target that meets all of these criteria has not yet been discovered in AML, CD123 has emerged as an attractive candidate. The first-in-class CD123-targeting agent, tagraxofusp-erzs (SL-401) was approved in 2018 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) and is currently in trials for several other hematologic malignancies, including AML. Several other CD123-targeted drugs are in development.