The abstract discusses the ongoing challenge of relapse in acute myeloid leukemia (AML) treatment, despite advancements. It highlights the potential of
natural killer (NK) cells in immunotherapy to treat
AML without the associated risks of
graft-versus-host disease or
cytokine release syndrome. The study reports that haploidentical NK cells, combined with high-dose chemotherapy and cytokine support, can lead to significant remissions in AML patients.
The text emphasizes the role of stress ligands like
MICA/B, which interact with the NK cell receptor
NKG2D, triggering NK cell activity against abnormal cells. It mentions clinical trials that have shown promise by developing NK cells with a NKG2D chimeric antigen receptor (CAR). However, it also notes the issue of
tumor cells evading NK cell detection by shedding the distal domains of MICA/B.
Researchers have identified the membrane-proximal α3 domain of MICA/B as a potential target for cancer immunotherapy. Given the heterogeneity of AML, the study suggests that dual-targeting strategies could improve clinical outcomes. The researchers have developed a Tri-specific Killer Engager (TriKE) that targets
CD33, a marker present on over 80% of AML cells, alongside
IL-15 to enhance NK cell response.
The study introduces a multiplexed-gene edited NK cell product derived from induced pluripotent stem cells (iPSCs). These cells express a high-affinity version of CD16, a membrane-bound IL-15 fusion receptor, and a CAR targeting the α3 domain of MICA/B. The product also includes
CD38 knockout to improve metabolic fitness.
Experiments showed that the iNK cells were effective against the AML cell line HL60, with enhanced activity when combined with the anti-CD33 TriKE. The α3 domain of MICA/B was confirmed as a target on AML cells, even after protease treatment. Dual-targeting with the α3 MICA/B CAR and anti-CD33 TriKE resulted in rapid and sustained killing of AML cells under both standard and stress conditions.
The abstract concludes that the combination of CAR NK cells targeting the α3 domain of MICA/B and antigen-specific TriKE targeting CD33 is a promising clinical approach to enhance the effectiveness and longevity of AML treatment. Ongoing studies are exploring the effects of drugs known to increase NKG2D ligands in AML.
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.
