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• W1493661170 endingPage "1273" @default.
• W1493661170 startingPage "1265" @default.
• W1493661170 abstract "The continuously growing natural killer (NK) cell line NK-92 is highly cytotoxic against malignant cells of various origins without affecting normal human cells. Based on this selectivity, the potential of NK-92 cells for adoptive therapy is currently being investigated in phase I clinical studies. To further enhance the antitumoral activity of NK-92 cells and expand the range of tumor entities suitable for NK-92–based therapies, here by transduction with a retroviral vector we have generated genetically modified NK-92 cells expressing a chimeric antigen receptor specific for the tumor-associated ErbB2 (HER2/neu) antigen, which is overexpressed by many tumors of epithelial origin. The chimeric antigen receptor consists of the ErbB2-specific scFv(FRP5) antibody fragment, a flexible hinge region derived from CD8, and transmembrane and intracellular regions of the CD3 ζ chain. Transduced NK-92-scFv(FRP5)-ζ cells express high levels of the fusion protein on the cell surface as determined by fluorescence-activated cell-scanning (FACS) analysis. In europium release assays, no difference in cytotoxic activity of NK-92 and NK-92-scFv(FRP5)-ζ cells toward ErbB2-negative targets was found. However, even at low effector-to-target ratios, NK-92-scFv(FRP5)-ζ cells specifically and efficiently lysed established and primary ErbB2-expressing tumor cells that were completely resistant to cytolytic activity of parental NK-92 cells. These results demonstrate that efficient retargeting of NK-92 cytotoxicity can be achieved and might allow the generation of potent cell-based therapeutics for the treatment of ErbB2-expressing malignancies." @default.
• W1493661170 created "2016-06-24" @default.
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• W1493661170 date "2002-08-15" @default.
• W1493661170 modified "2023-10-01" @default.
• W1493661170 title "Retargeting of natural killer–cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction" @default.
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• W1493661170 doi "https://doi.org/10.1182/blood.v100.4.1265.h81602001265_1265_1273" @default.
• W1493661170 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12149207" @default.
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