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    • 3. 发明公开
    • ONCOLYTIC ADENOVIRUS FOR TARGET THERAPY OF HUMAN TUMOR AND USE THEREOF
    • 对人类肿瘤溶瘤腺病毒治疗的目的及其用途
    • EP2682459A4
    • 2014-12-10
    • EP12752828
    • 2012-02-29
    • BEIJING BIO TARGETING THERAPEUTICS TECHNOLOGY INC
    • WANG YAOHEJIANG GUOZHONGWANG PENGJUGAO DONGLINGLEMOINE NICK
    • C12N7/01A61K31/711A61K35/76A61K38/00A61K48/00C07K14/54C12N15/24C12N15/86C12N15/861
    • A61K31/711A61K35/761A61K38/00C07K14/5434C12N15/86C12N2710/10332C12N2710/10343
    • Provided is an oncolytic adenovirus Ad-TD-hIL12 for target therapy of human tumor, which is deposited in China Center for Type Culture Collection with an accession number CCTCC NO: V201031. The viral vector is C-subclass type 5 adenovirus Ads, which has three genes E1A-CR2, E1B19K and E3gp-19K deleted, and expresses p35 and p40 subgroup gene sequences of human IL12 under the control of the E3gp-19K promoter. Oncolytic cells are replicated in tumor cells by infecting the tumor cells with the viruses, and at the same time, hIL2 having a variety of anti-tumor effects is produced in the tumor tissue at a high level. hIL12 has the effect of anti-tumor angiogenesis, can regulate the body's immunity to make the body produce specific anti-tumor immunity, kill distant metastatic tumor cells, and prevent tumor recurrence. The viral vector of the present invention can be used as a targeting genetic engineering drug for treating various solid tumors, not only can be used for intratumoral injection, can also be used for intraperitoneal and intrathoracic injection, without causing significant side effects, thus having better efficacy and safety.
    • 本发明提供一种溶瘤腺病毒,其在中国的中心沉积的典型培养物保藏CCTCC NO的登录号的Ad-TD-hIL12为人类肿瘤的靶向治疗,所有:V201031。 所述病毒载体是C-子类5型腺病毒广告,其中有三个基因E1A-CR2,E1B19K和E3gp-19K删除,和人IL-12的E3gp-19K启动子的控制下,快车的p35和p40亚组的基因序列。 溶瘤细胞在肿瘤细胞中通过与病毒感染肿瘤细胞复制,并且在在Sametime,被在肿瘤组织中以高水平产生具有各种抗肿瘤作用HIL2。 hIL12具有抗肿瘤血管生成的作用,可以调节人体的免疫力,使身体产生特异性的抗肿瘤免疫,杀远处转移肿瘤细胞,和防止肿瘤复发。 本发明的病毒载体可以用作靶向基因工程药物用于治疗各种实体瘤,不仅可用于瘤内注射,因此可以用于腹膜内和胸腔内注射,而不引起显著的副作用,因此具有更好的 疗效和安全性。
    • 6. 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。