Enhanced Cytotoxicity and Survival Benefits of FLT3 CAR-NK Cells in Acute Myeloid Leukemia Treatment
The study involved the transduction of cord blood NK cells with FLT3 CAR constructs featuring CD28/CD3ζ or 2B4/CD3ζ, which showed comparable cytotoxicity against FLT3+ AML cells both in vitro and in vivo. When these NK cells were transduced with soluble or membrane-bound IL-15, they demonstrated extended survival and superior performance compared to other transduced NK cells. Notably, only the soluble IL-15-transduced NK cells could activate neighboring non-transduced NK and T cells in a paracrine manner.
The FLT3 CAR_s15 NK cells expanded significantly ex vivo, with a substantial proportion expressing both the FLT3 CAR and soluble IL-15. These cells exhibited heightened cytotoxicity and IFN-γ production when tested against the FLT3+ AML cell line MOLM-13. Post-thaw, these cells maintained high recovery, viability, and functionality, closely resembling fresh FLT3 CAR_s15 NK cells.
In vivo testing using immunodeficient mice with the MOLM-13 FLT3+ cell line revealed that infusions of FLT3 CAR_s15 NK cells significantly improved median survival rates. Additionally, the cells did not exhibit undue cytotoxicity against normal peripheral blood mononuclear cells (PBMC), including FLT3+ dendritic cells, or disrupt hematopoietic stem cell (HSC) differentiation in vivo.
The findings collectively suggest that allogeneic, off-the-shelf cord blood-derived FLT3 CAR_s15 NK cells have enhanced cytotoxicity and IFN-γ secretion against FLT3+ AML, and they improve the survival of mice with FLT3+ AML without causing PBMC or HSC toxicity. This supports the potential of investigating FLT3 CAR_s15 NK cell therapy as a novel treatment for patients with FLT3+ 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.
