CD123

Class

CD123-targeted recombinant fusion protein toxin (IL-3 fused to truncated diphtheria toxin)

Pathway

CD123-mediated internalization followed by ADP-ribosylation of eEF2, halting protein synthesis and inducing apoptosis

Notes

original target text: CD123 (IL3RA)

CD123, also known as the interleukin-3 receptor alpha chain (IL3RA), is a cell-surface receptor expressed at low levels on normal blood-forming cells but markedly elevated on the malignant cells of certain blood cancers, including blastic plasmacytoid dendritic cell neoplasm and acute myeloid leukemia. Because this overexpression is relatively selective, CD123 has become an attractive handle for directing cytotoxic payloads specifically to malignant cells while limiting exposure to healthy tissue. One engineering approach fuses the receptor's natural ligand, interleukin-3, to a truncated bacterial toxin derived from diphtheria toxin. When this fusion protein binds CD123, the complex is taken into the cell through receptor-mediated internalization; once inside, the toxin portion chemically modifies a protein synthesis factor, halting the cell's ability to make new proteins and triggering programmed cell death. This mechanism does not depend on triggering the receptor's normal growth-signaling function, but rather exploits it purely as an entry point for the toxin. Beyond toxin fusions, CD123 is also targeted by antibody-drug conjugates, chimeric antigen receptor cell therapies, and other engineered constructs, reflecting broad interest in this receptor across modalities for hematologic malignancies where leukemic stem cells and blasts depend on its expression.