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新型抗血管生成病毒疗法VB - 111在甲状腺癌异种移植小鼠模型中的抗肿瘤活性

Antitumor Activity of VB-111, a Novel Antiangiogenic Virotherapeutic, in Thyroid Cancer Xenograft Mouse Models.

作者信息

Reddi H V, Madde P, Cohen Y C, Bangio L, Breitbart E, Harats D, Bible K C, Eberhardt N L

机构信息

Department of Medicine, Division of Endocrinology, Mayo Clinic, Rochester, MN, USA.

出版信息

Genes Cancer. 2011 Oct;2(10):993-5. doi: 10.1177/1947601912437933.

Abstract

VB-111 is an engineered antiangiogenic adenovirus that expresses Fas-c in angiogenic blood vessels and has previously been shown to have significant antitumor activity in vitro and in vivo in Lewis lung carcinoma, melanoma, and glioblastoma models. To evaluate the efficacy of VB-111 in thyroid cancer, we conducted in vivo xenograft nude mouse studies using multiple thyroid cancer-derived cell lines models. VB-111 treatment resulted in 26.6% (P = 0.0596), 34.4% (P = 0.0046), and 37.6% (P = 0.0249) inhibition of tumor growth in follicular, papillary and anaplastic thyroid cancer models, respectively. No toxicity was observed in any model. All tumor types showed a consistent and significant reduction of CD-31 staining (P < 0.05), reflecting a reduction of angiogenic activity in the tumors, consistent with the intended targeting of the virus. A phase 2 clinical trial of VB-111 in patients with advanced differentiated thyroid cancer is ongoing.

摘要

VB - 111是一种经过基因工程改造的抗血管生成腺病毒,可在血管生成的血管中表达Fas - c,此前已证明其在Lewis肺癌、黑色素瘤和胶质母细胞瘤模型的体外和体内实验中具有显著的抗肿瘤活性。为了评估VB - 111在甲状腺癌中的疗效,我们使用多种源自甲状腺癌的细胞系模型进行了体内异种移植裸鼠研究。VB - 111治疗分别在滤泡性、乳头状和未分化甲状腺癌模型中导致肿瘤生长抑制26.6%(P = 0.0596)、34.4%(P = 0.0046)和37.6%(P = 0.0249)。在任何模型中均未观察到毒性。所有肿瘤类型均显示CD - 31染色一致且显著减少(P < 0.05),这反映出肿瘤血管生成活性降低,与该病毒的预期靶向作用相符。VB - 111在晚期分化型甲状腺癌患者中的2期临床试验正在进行。

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VB-111 for cancer.VB-111 治疗癌症。
Expert Opin Biol Ther. 2011 Dec;11(12):1669-76. doi: 10.1517/14712598.2011.618122. Epub 2011 Oct 1.
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Endocr Relat Cancer. 2010 Jan 29;17(1):61-72. doi: 10.1677/ERC-08-0251. Print 2010 Mar.
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Curr Treat Options Oncol. 2000 Oct;1(4):353-7. doi: 10.1007/s11864-000-0051-8.

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