The
CD123 antigen is present in several
blood-related cancers, such as
AML, MDS,
B-ALL, and others. Notably, in AML, CD123 is predominantly found on AML cells, particularly on stem cells that are more primitive, suggesting a potential therapeutic target. A mouse antibody, 7G3, which inhibits
IL-3 binding to CD123, was found to be effective against human AML stem cells in mice, leveraging both innate immune system engagement and other mechanisms.
Further development led to the creation of
CSL362, a humanized and enhanced antibody. This antibody not only neutralizes IL-3 but also has a stronger binding affinity to the
FcγRIIIa receptor on NK cells, which is linked to improved cell-killing efficacy. In vitro tests have shown that CSL362 is more effective at eliminating CD123-positive cell lines compared to a non-engineered version. Importantly, it can also target primary AML cells and stem cells, even those resistant to non-engineered antibodies.
In a mouse model of AML, CSL362 demonstrated superior efficacy in slowing down
cancer growth. NK cells were identified as the primary mediators of CSL362's cytotoxic effects. Clinical samples also showed that CSL362 can deplete AML cells when combined with patient-derived immune cells, indicating that the NK cells' function is preserved enough for targeted cell killing.
The accumulated pre-clinical evidence supports advancing CSL362 into clinical trials for AML treatment, particularly for patients with functional NK cells. A Phase 1 clinical trial for
CD123-positive AML patients in remission is currently in progress, as registered on Clinical Trials.gov.
How to Use Synapse Database to Search and Analyze Translational Medicine Data?
The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

Click on the image below to go directly to the Translational Medicine search interface.
