title: HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo.
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.
authors.affiliation: Department of Neurosurgery, PLA Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Leiming
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, PLA Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Junlin
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Hangyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, PLA Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Shuangwu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, PLA Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, PLA Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Dandong
authors.initials: D
authors.lastname: Fang
authors.affiliation: Department of Neurosurgery, PLA Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Angang
authors.initials: A
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016466:CHO Cells; D053178:Caspase 6 / Q000235:genetics*; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D053178:Caspase 6; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C508053:ERBB2 protein, human; C505514:CASP6 protein, human