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**123NL CAR-T** is an investigational dual-target CAR-T-cell therapy developed at Tianjin First Central Hospital for relapsed or refractory CD123-positive acute myeloid leukemia. The engineered T cells co-recognize CD123, the alpha subunit of the interleukin-3 receptor expressed on AML blasts and leukemic stem cells, and NKG2D ligands expressed on malignant cells and immunosuppressive myeloid cells. Its CD123-binding single-chain variable fragment is derived from clone 7G3, while NKG2D-ligand recognition uses the NKG2D extracellular domain. The product is designed to kill AML cells while also depleting immunosuppressive monocyte-like myeloid-derived suppressor cells and M2 macrophages, potentially reducing antigen escape and microenvironment-mediated resistance. The CAR construct also incorporates RQR8, a marker/suicide element that can enable rituximab-mediated elimination of the infused CAR-T cells. A prospective exploratory clinical study in AML is registered as ChiCTR1900028040. ([chictr.org.cn](https://www.chictr.org.cn/showproj.html?proj=46574))
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