Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system.
Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system.
复制标题
DOI：
10.1038/s41598-017-14717-x
复制
发表时间：
2017-10-26
影响因子：
4.6
通讯作者：
Fujiwara T
中科院分区：
文献类型：
--
作者：
Aoyama K;Kuroda S;Morihiro T;Kanaya N;Kubota T;Kakiuchi Y;Kikuchi S;Nishizaki M;Kagawa S;Tazawa H;Fujiwara T
溶瘤病毒疗法的缺点是由于免疫消除而不适合全身递送。脂质体包封是公认的减少免疫消除和提高药物在血液中的稳定性。在本研究中，脂质体包裹的表达GFP （lipop - pts）的端粒酶特异性溶瘤腺病毒（TelomeScan）的质粒DNA作为一种适合全身递送的溶瘤腺病毒药物的潜力进行了研究。lipop - pts直径为40-50 nm，在体外和体内均对HCT116结肠癌细胞有较强的抗肿瘤作用。脂质体的肿瘤选择性与柯萨奇和腺病毒受体（CAR）无关。重要的是，与TelomeScan相比，lipop - pts在静脉给药到免疫能力小鼠后减少了腺病毒中和抗体（adnab）的产生，即使在adnab存在的情况下，lipop - pts也保持了很强的细胞毒性。综上所述，lipop - pts有潜力成为一种适合全身递送的溶瘤腺病毒药物，具有不依赖car的抗肿瘤活性和对免疫系统的隐身作用。
Oncolytic virotherapy has the disadvantage of being unsuitable for systemic delivery due to immune elimination. Liposomal encapsulation is well-recognized to reduce immune elimination and enhance the stability of drugs in the bloodstream. In the present study, the potential of liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus (TelomeScan) expressing GFP (Lipo-pTS) as an oncolytic adenoviral agent suitable for systemic delivery was investigated. Lipo-pTS, which has a diameter of 40–50 nm, showed potent antitumor effects on HCT116 colon carcinoma cells in vitro and in vivo. Tumor selectivity of Lipo-pTS was independent of coxsackie and adenovirus receptor (CAR). Importantly, Lipo-pTS reduced production of adenovirus-neutralizing antibodies (AdNAbs) after intravenous administration into immune-competent mice compared to TelomeScan, and even in the presence of AdNAbs, Lipo-pTS maintained strong cytotoxicity. In conclusion, Lipo-pTS has the potential to become an oncolytic adenoviral agent suitable for systemic delivery with the characteristics of CAR-independent antitumor activity and a stealth effect on the immune system.
登录
查看更多内容
影响因子：
14
作者：
Mendez, Natalie;Herrera, Vanessa;Zhang, Lingzhi;Hedjran, Farah;Feuer, Ralph;Blair, Sarah L.;Trogler, William C.;Reid, Tony R.;Kummel, Andrew C.
通讯作者：
Kummel, Andrew C.
影响因子：
2.2
作者：
Ferguson MS;Lemoine NR;Wang Y
通讯作者：
Wang Y
用于基因递送的纳米粒子的生产和临床开发
DOI：
10.1038/mtm.2016.23
发表时间：
2016
期刊：
Molecular therapy. Methods & clinical development
影响因子：
--
作者：
Chen J;Guo Z;Tian H;Chen X
通讯作者：
Chen X
影响因子：
6.4
作者：
Fujiwara, Toshiya;Kagawa, Shunsuke;Fujiwara, Toshiyoshi
通讯作者：
Fujiwara, Toshiyoshi
影响因子：
10.8
作者：
Kwon, Oh-Joon;Kang, Eunah;Yun, Chae-Ok
通讯作者：
Yun, Chae-Ok