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Article

HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo

  • Authors:
    • Leiming Zhang
    • Junlin Ren
    • Hangyu Zhang
    • Gang Cheng
    • Yanming Xu
    • Shuangwu Yang
    • Chao Dong
    • Dandong Fang
    • Jianning Zhang
    • Angang Yang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, PLA Navy General Hospital, Beijing 100048, P.R. China, Department of Clinical Laboratory, PLA Navy General Hospital, Beijing 100048, P.R. China, Department of Hepatobiliary Surgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Xi'an, Shaanxi 710032, P.R. China, State Key Laboratory of Cancer Biology, Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
  • Pages: 2689-2696
    |
    Published online on: September 12, 2016
       https://doi.org/10.3892/or.2016.5088
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Abstract

Glioblastoma multiforme (GBM), which is associated with a high rate of morbidity and mortality, is among the most malignant and treatment-refractory neoplasms in human adults. As GBM is highly resistant to conventional therapies, immunotherapies are a promising treatment candidate. HER2 is an attractive target for GBM immunotherapy, as its expression is highly associated with various types of GBM. We previously reported that a novel HER2-targeted recombinant protein e23sFv-Fdt-casp6 has an antitumor effect on HER2-positive gastric cancer cells. In this study, we established a genetically modified Chinese hamster ovary cell line, which produced and secreted e23sFv-Fdt-casp6 proteins. Following specific binding to and internalization into HER2-overexpressing tumor cells, the e23sFv-Fdt-casp6 protein induced tumor cell apoptosis and inhibited the proliferation of HER2-overexpressing A172 and U251MG cells in vitro, but not in U87MG cells with undetectable HER2. The e23sFv-Fdt-casp6 gene was introduced into severe combined immunodeficient mice bearing human glioblastoma xenografts by using intramuscular injections of a liposome-encapsulated vector. The recombinant protein e23sFv-Fdt-casp6 specifically targeted tumor cells and induced apoptosis, thereby leading to potent inhibition of tumor growth and prolonged the survival time of tumor-bearing mice. We concluded that e23sFv‑Fdt‑casp6 represents a promising HER2-targeted treatment option for human gliomas.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang L, Ren J, Zhang H, Cheng G, Xu Y, Yang S, Dong C, Fang D, Zhang J, Yang A, Yang A, et al: HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo. Oncol Rep 36: 2689-2696, 2016.
APA
Zhang, L., Ren, J., Zhang, H., Cheng, G., Xu, Y., Yang, S. ... Yang, A. (2016). HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo. Oncology Reports, 36, 2689-2696. https://doi.org/10.3892/or.2016.5088
MLA
Zhang, L., Ren, J., Zhang, H., Cheng, G., Xu, Y., Yang, S., Dong, C., Fang, D., Zhang, J., Yang, A."HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo". Oncology Reports 36.5 (2016): 2689-2696.
Chicago
Zhang, L., Ren, J., Zhang, H., Cheng, G., Xu, Y., Yang, S., Dong, C., Fang, D., Zhang, J., Yang, A."HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo". Oncology Reports 36, no. 5 (2016): 2689-2696. https://doi.org/10.3892/or.2016.5088
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang L, Ren J, Zhang H, Cheng G, Xu Y, Yang S, Dong C, Fang D, Zhang J, Yang A, Yang A, et al: HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo. Oncol Rep 36: 2689-2696, 2016.
APA
Zhang, L., Ren, J., Zhang, H., Cheng, G., Xu, Y., Yang, S. ... Yang, A. (2016). HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo. Oncology Reports, 36, 2689-2696. https://doi.org/10.3892/or.2016.5088
MLA
Zhang, L., Ren, J., Zhang, H., Cheng, G., Xu, Y., Yang, S., Dong, C., Fang, D., Zhang, J., Yang, A."HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo". Oncology Reports 36.5 (2016): 2689-2696.
Chicago
Zhang, L., Ren, J., Zhang, H., Cheng, G., Xu, Y., Yang, S., Dong, C., Fang, D., Zhang, J., Yang, A."HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo". Oncology Reports 36, no. 5 (2016): 2689-2696. https://doi.org/10.3892/or.2016.5088
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