Adenovirus-mediated REIC/Dkk-3 gene therapy: Development of an autologous cancer vaccination therapy (Review).

Adenovirus-mediated REIC/Dkk-3 gene therapy: Development of an autologous cancer vaccination therapy (Review).
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DOI:
10.3892/ol.2013.1777
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发表时间:
2014-03
期刊:
影响因子:
2.9
通讯作者:
Kumon H
Kumon H
中科院分区:
医学4区
文献类型:
--
作者:
Watanabe M;Nasu Y;Kumon H

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在永生化细胞中表达减少(REIC)/Dickkopf(Dkk)-3是一种肿瘤抑制和治疗基因,并且已经就癌症基因治疗的应用进行了研究。我们以前的研究表明,肿瘤内注射携带人REIC/Dkk-3基因的腺病毒载体(Ad-REIC)抑制前列腺癌、乳腺癌、睾丸癌和恶性间皮瘤小鼠模型中的肿瘤生长。这些抗肿瘤治疗作用的机制最近才得到澄清。已经证明,Ad-REIC治疗通过上调全身抗癌免疫抑制癌症进展。在实验条件下,通过癌症特异性细胞凋亡和抗癌免疫激活的自体癌症疫苗接种是一种可能的治疗机制。在先前的临床前研究中观察到的稳健的抗癌作用支持Ad-REIC的临床效用。目前,Ad-REIC基因治疗前列腺癌患者的I-IIa期研究正在进行中。本研究回顾了以往基础研究的观察结果,并总结了肿瘤内Ad-REIC治疗癌症疫苗的抗癌机制。
Reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3 is a tumor suppressor and therapeutic gene and has been studied with respect to the application of cancer gene therapy. Our previous studies demonstrated that the intratumoral injection of an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC) suppresses tumor growth in mouse models of prostate, breast and testicular cancer and malignant mesothelioma. The mechanisms underlying these antitumor therapeutic effects have only been clarified recently. It has been demonstrated that Ad-REIC treatment inhibits cancer progression via the upregulation of systemic anticancer immunity. Under experimental conditions, autologous cancer vaccination via cancer-specific apoptosis and anticancer immune activation is a possible therapeutic mechanism. The robust anticancer effects observed in previous preclinical studies support the clinical utility of Ad-REIC. At present, a phase I–IIa study of Ad-REIC gene therapy in prostate cancer patients is ongoing. The current study reviews the observations of previous fundamental studies and summarizes the anticancer mechanisms of intratumoral Ad-REIC treatment in terms of cancer vaccination.
全细胞癌症疫苗:从自体到同种异体肿瘤和基于树突状细胞的疫苗。
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