HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo.
HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo.
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HER2 靶向重组蛋白免疫 caspase-6 可在体外和体内有效诱导 HER2 过表达 GBM 细胞凋亡。
DOI：
10.3892/or.2016.5088
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发表时间：
2016
期刊：
影响因子：
4.2
通讯作者：
A. Yang
中科院分区：
文献类型：
--
作者：
Lei;Jun;Hangyu Zhang;G. Cheng;Yan Xu;Shuangwu Yang;Chao Dong;Dandong Fang;Jianning Zhang;A. Yang
多形性胶质母细胞瘤(GBM)是成人最恶性、最难治疗的肿瘤之一，具有较高的发病率和死亡率。由于GBM对传统疗法高度耐药，免疫疗法是一种很有前途的治疗方案。HER2的表达与多种类型的GBM密切相关，是GBM免疫治疗的一个有吸引力的靶点。我们先前报道了一种新的针对HER2的重组蛋白e23sFv-FDT-casp6对HER2阳性的胃癌细胞具有抗肿瘤作用。在本研究中，我们建立了一个转基因的中国仓鼠卵巢细胞系，该细胞系能够产生和分泌e23sFv-FDT-casp6蛋白。E23sFv-FDT-casp6蛋白与HER2高表达的肿瘤细胞特异性结合并内化后，在体外诱导肿瘤细胞凋亡并抑制HER2高表达的A172和U251 MG细胞的增殖，但对未检测到HER2的U87 MG细胞无明显影响。通过肌肉注射脂质体包裹载体，将e23sFv-FDT-casp6基因导入携带人胶质母细胞瘤移植瘤的严重联合免疫缺陷小鼠体内。重组蛋白e23sFv-FDT-casp6可特异性靶向肿瘤细胞，诱导肿瘤细胞凋亡，从而有效抑制肿瘤生长，延长荷瘤小鼠的生存时间。我们的结论是，e23sFv-FDT-casp6是一种有希望的HER2靶向治疗人脑胶质瘤的选择。
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.
DOI：
10.1073/pnas.89.6.2287
发表时间：
1992-03-15
影响因子：
11.1
作者：
LUPU, R;COLOMER, R;LIPPMAN, ME
通讯作者：
LIPPMAN, ME
阿魏酸通过调节上皮间质转化发挥抗肿瘤活性并抑制乳腺癌细胞的转移
影响因子：
4.2
作者：
Zhang, Xiang;Lin, Dan;Li, Hongyuan
通讯作者：
Li, Hongyuan
影响因子：
5.5
作者：
Kim, Daejin;Hung, Chien-Fu;Wu, T. -C.;Park, Yeong-Min
通讯作者：
Park, Yeong-Min