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NK92MI + HN3 is a combination cell therapy consisting of genetically engineered NK92MI cells expressing a third-generation chimeric antigen receptor (CAR) constructed using HN3, a human single-domain antibody targeting a conformational epitope on the core protein of glypican-3 (GPC3). NK92MI is an IL-2-independent natural killer cell line capable of indefinite expansion. The CAR construct incorporates signaling domains CD28, 4-1BB ligand, and CD3 zeta, designed to enhance cytotoxicity. The principal indication is for **hepatocellular carcinoma (HCC)**, for which GPC3 is highly expressed. NK92MI/HN3 shows significant anti-tumor activity against GPC3-positive HCC cells in vitro and inhibits tumor growth in xenograft mouse models. Its cytotoxicity is influenced by GPC3 isoform expression. Primary mechanism involves targeted lysis of GPC3-expressing tumor cells via CAR-mediated recognition and NK effector functions, with increased production of IFN-γ and expression of CD107a upon engagement.
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