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    • 1. 发明公开
    • CONSTRUCTION AND APPLICATION OF MUTANT TYPE B HUMAN ADENOVIRUS AD11 HAVING ENHANCED ONCOLYTIC POWER
    • 建设和突变的人类腺病毒AD11 TYPE B的性能得到改善溶瘤应用
    • EP2716764A4
    • 2015-01-14
    • EP12792810
    • 2012-02-29
    • BEIJING BIO TARGETING THERAPEUTICS TECHNOLOGY INC
    • WANG YAOHEJIANG HANSHIWONG HANSHICAO FENGYULEMOINE NICK
    • C12N15/861A61K48/00A61P35/00C12N15/66C12R1/93
    • C12N15/86A61K35/761C12N7/00C12N2710/10321C12N2710/10332C12N2710/10343
    • A method for constructing type-B recombinant human adenoviral vectors Ad11-5EP and Ad11-5ETel-GFP, and applications thereof. Construction of the adenoviral vector Ad11-5EP utilizes homologous recombination to substitute a 365 bp-long gene upstream segment of the Ad5 E1A coding sequence (comprising the enhancer and promoter of Ad5 E1A) to the corresponding region of type-B human adenovirus subtype 11 Ad11, thereby constructing said vector Ad11-5EP. The method for constructing the type-B recombinant human adenoviral vectorAd11-5ETel-GFP is simultaneous homologous recombination of the genomes of the constructed shuttle vectors pSSENTel, pSSGFP and Ad11-5EP, so as to produce said Ad11-5ETel-GFP. Vector Ad11-5EP possesses a stronger oncolytic effect than the wild-type Ad11, which enhances the power to kill tumor cells. Measurements of tumour growth and tumour clearance rates show that Ad11-5EP effectively reduces tumour growth rates, while the tumour-free ratio among tumour-bearing mice using AdII-5EP is noticeably better than for Ad11. Constructed Ad11-SETel-GFP can be used for treating tumours, or for specific, sensitive and economical detection of tumour cells in circulating blood.
    • 一种用于构造类型B的重组人腺病毒载体Ad11-5EP和Ad11-5ETel-GFP,和其应用方法。 所述腺病毒载体Ad11-5EP的构建利用同源重组以替代的Ad5 E1A的365 bp的基因长上游区段的编码序列(包括Ad5的E1A的增强子和启动子)以B型人类腺病毒亚型11 AD11的相应区域 ,从而构建所述载体Ad11-5EP。 构建B型重组人腺病毒vectorAd11-5ETel-GFP的方法是构建穿梭的基因组的同时同源重组载体pSSENTel,pSSGFP和Ad11-5EP以便产生所述Ad11-5ETel GFP。 矢量Ad11-5EP拥有比野生型AD11,从而增强杀死肿瘤细胞的动力更强的杀伤效果。 的肿瘤生长和肿瘤清除率测量显示没有Ad11-5EP有效地降低肿瘤的生长速率,同时使用ADII-5EP荷瘤小鼠中的无肿瘤比率明显比为AD11更好。 构造AD11-SETEL-GFP可以用于治疗肿瘤,或用于循环血液的肿瘤细胞的特异性的,灵敏的和经济的检测。