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A novel, polymer-coated oncolytic measles virus overcomes immune suppression and induces robust antitumor activity.
Molecular Therapy - Oncolytics ( IF 5.7 ) Pub Date : 2016-11-17 , DOI: 10.1038/mto.2016.22
Kaname Nosaki 1 , Katsuyuki Hamada 2 , Yuto Takashima 3 , Miyako Sagara 3 , Yumiko Matsumura 3 , Shohei Miyamoto 4 , Yasuki Hijikata 3 , Toshihiko Okazaki 3 , Yoichi Nakanishi 5 , Kenzaburo Tani 4
Affiliation  

Although various therapies are available to treat cancers, including surgery, chemotherapy, and radiotherapy, cancer has been the leading cause of death in Japan for the last 30 years, and new therapeutic modalities are urgently needed. As a new modality, there has recently been great interest in oncolytic virotherapy, with measles virus being a candidate virus expected to show strong antitumor effects. The efficacy of virotherapy, however, was strongly limited by the host immune response in previous clinical trials. To enhance and prolong the antitumor activity of virotherapy, we combined the use of two newly developed tools: the genetically engineered measles virus (MV-NPL) and the multilayer virus-coating method of layer-by-layer deposition of ionic polymers. We compared the oncolytic effects of this polymer-coated MV-NPL with the naked MV-NPL, both in vitro and in vivo. In the presence of anti-MV neutralizing antibodies, the polymer-coated virus showed more enhanced oncolytic activity than did the naked MV-NPL in vitro. We also examined antitumor activities in virus-treated mice. Complement-dependent cytotoxicity and antitumor activities were higher in mice treated with polymer-coated MV-NPL than in mice treated with the naked virus. This novel, polymer-coated MV-NPL is promising for clinical cancer therapy in the future.

中文翻译:

一种新型的聚合物包被的溶瘤性麻疹病毒克服了免疫抑制作用,并诱导了强大的抗肿瘤活性。

尽管可以使用多种疗法来治疗癌症,包括手术,化学疗法和放射疗法,但是在过去的30年中,癌症一直是日本的主要死亡原因,因此迫切需要新的治疗方法。作为一种新形式,近来对溶瘤病毒疗法引起了极大的兴趣,麻疹病毒是有望显示出强大抗肿瘤作用的候选病毒。然而,在先前的临床试验中,病毒疗法的功效受到宿主免疫反应的强烈限制。为了增强和延长病毒疗法的抗肿瘤活性,我们结合使用了两种新开发的工具:基因工程麻疹病毒(MV-NPL)和离子聚合物逐层沉积的多层病毒包被方法。我们将这种聚合物涂层的MV-NPL与裸露的MV-NPL的溶瘤作用进行了比较,无论是体内还是体外。在存在抗MV中和抗体的情况下,与裸露的MV-NPL相比,聚合物包被的病毒显示出更高的溶瘤活性。我们还检查了病毒治疗小鼠的抗肿瘤活性。用聚合物包被的MV-NPL处理的小鼠的补体依赖性细胞毒性和抗肿瘤活性高于用裸病毒处理的小鼠。这种新颖的,聚合物涂层的MV-NPL有望在将来用于临床癌症治疗。用聚合物包被的MV-NPL处理的小鼠的补体依赖性细胞毒性和抗肿瘤活性高于用裸病毒处理的小鼠。这种新颖的,聚合物涂层的MV-NPL有望在将来用于临床癌症治疗。用聚合物包被的MV-NPL处理的小鼠的补体依赖性细胞毒性和抗肿瘤活性高于用裸病毒处理的小鼠。这种新颖的,聚合物涂层的MV-NPL有望在将来用于临床癌症治疗。
更新日期:2019-11-01
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