Specific growth inhibition of ErbB2‑expressing human breast cancer cells by genetically modified NK‑92 cells

Liu,Hui; Yang,Bo; Sun,Tingting; Lin,Lin; Hu,Yi; Deng,Muhong; Yang,Junlan; Liu,Tianyi; Li,Jinyu; Sun,Shengjie; Jiao,Shunchang

doi:10.3892/or.2014.3548

Specific growth inhibition of ErbB2‑expressing human breast cancer cells by genetically modified NK‑92 cells

Authors:
- Hui Liu
- Bo Yang
- Tingting Sun
- Lin Lin
- Yi Hu
- Muhong Deng
- Junlan Yang
- Tianyi Liu
- Jinyu Li
- Shengjie Sun
- Shunchang Jiao
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Affiliations: Department of Internal Oncology, 301 General Hospital, Beijing, P.R. China, Department of Internal Neurology, Hainan Branch of 301 General Hospital, Hainan, P.R. China, Tumor Central Laboratory, 301 General Hospital, Beijing, P.R. China
Published online on: October 17, 2014 https://doi.org/10.3892/or.2014.3548
Pages: 95-102

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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 receptor by optimized electroporation 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.

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