title: Specific growth inhibition of ErbB2‑expressing human breast cancer cells by genetically modified NK‑92 cells.
abstract: The natural killer cell line NK‑92 shows great cytotoxicity against various types of cancer. Several types of solid tumor cells, however, can effectively resist NK-mediated lysis by interaction of major histocompatibility complex (MHC) molecules with NK cell inhibitory receptors. To generate a eukaryotic expression vector encoding chimeric antigen receptor scFv anti-erbB2-CD28-ζ and to investigate the expression and action of this chimeric antigen receptor in cancer cells both in vitro and in vivo, NK‑92 cells were genetically modified with an scFv anti-erbB2-CD28-ζ chimeric recep-tor by optimized electro-poration using the Amaxa Nucleofector system. The expression of the chimeric receptor was evaluated by RT-PCR and immunofluorescence. The ability of the genetically modified NK‑92 cells to induce cell death in tumor targets was assessed in vitro and in vivo. The transduced NK‑92-anti-erbB2 scFv-CD28-ζ cells expressing high levels of the fusion protein on the cell surface were analyzed by fluorescence-activated cell-sorting (FACS) analysis. These cells specifically enhanced the cell death of the erbB2‑expressing human breast cancer cell lines MDA-MB-453 and SKBr3. Furthermore, adoptive transfer of genetically modified NK‑92 cells specifically reduced tumor size and lung metastasis of nude mice bearing established MDA-MB-453 cells, and significantly enhanced the survival period of these mice. The genetically modified NK‑92 cells significantly enhanced the killing of erbB2‑expressing cancer and may be a novel therapeutic strategy for erbB2‑expressing cancer cells.
authors.affiliation: Department of Internal Oncology, 301 General Hospital, Beijing, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Internal Oncology, 301 General Hospital, Beijing, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Internal Neurology, Hainan Branch of 301 General Hospital, Hainan, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Internal Oncology, 301 General Hospital, Beijing, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Internal Oncology, 301 General Hospital, Beijing, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Internal Oncology, 301 General Hospital, Beijing, P.R. China.
authors.forename: Muhong
authors.initials: M
authors.lastname: Deng
authors.affiliation: Department of Internal Oncology, 301 General Hospital, Beijing, P.R. China.
authors.forename: Junlan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Tumor Central Laboratory, 301 General Hospital, Beijing, P.R. China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Internal Oncology, 301 General Hospital, Beijing, P.R. China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Internal Oncology, 301 General Hospital, Beijing, P.R. China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Internal Oncology, 301 General Hospital, Beijing, P.R. China.
authors.forename: Shunchang
authors.initials: S
authors.lastname: Jiao
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D047368:Tumor Burden
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human