CD123 is overexpressed in many hematologic malignancies, including blastic plasmocytoid dendritic neoplasm (BPDCN)s, Acute Myeloblastic Leukemias (AMLs), B-acute lymphocytic leukemias, Hairy Cell Leukemia. Importantly, in some of these conditions, such as AMLs, the high expression of CD123 is a feature of leukemic stem cells, making very attractive the opportunity to therapeutically target this membrane receptor. Therefore, various agents have been developed in an attempt to use CD123 targeting to kill leukemic cells overexpressing this receptor, either using a fusion protein formed by recombinant IL3 fused to diphteria toxin (SL401) or a humanized neutralizing anti-CD123 monoclonal antibody or T cells transduced withg a retroviral vector encoding an anti-CD123 chimeric antigen receptor. Some of these compounds were introduced in clinical studies in the context of phase I studies in AML and BPDCN patients with promising results. Additional studies will be required to assess the role of these CD123-targeting drugs, not only when used alone, but also in combination with standard anti-leukemic drugs in the treatment of various leukemic cionditions. Furthermore, it would be particularly interesting to assess the possible therapeutic impact of CD123-targeting drugs to attempt the treatment of minimal residual disease.
Drug targets for cancer: CD123 research reagents
Other vital drug targets for cancer likeCD123:
Deckert J, et al. A novel anti-CD37 antibody-drug conjugate with multiple anti-tumor mechanisms for the treatment of B-cell malignancies[J]. Blood, 2013, 122(20): 3500-3510.