NKAR.2

NKAR.2 is a second-generation chimeric antigen receptor (CAR) construct specifically engineered for Natural Killer (NK) cells to treat hematological malignancies, including acute myeloid leukemia (AML) and B-cell lymphomas. The construct utilizes the extracellular domain of the NKG2D receptor for the recognition of stress-induced NKG2D ligands (NKG2DLs) on tumor cells. Its intracellular architecture is optimized for NK cell biology, incorporating the NKG2D transmembrane domain, a 2B4 (CD244) costimulatory domain, and a CD3ζ signaling domain. Preclinical studies indicate that this configuration (N.N.2B4.z) provides superior cytotoxic activity in NK-92 and YTS cell lines compared to traditional T-cell-optimized CARs. NKAR.2 is often studied in combination with bispecific killer cell engagers (NKABs) to enhance tumor targeting and overcome immune evasion mechanisms such as ligand shedding or antigen loss.