CONSTRUCTION AND APPLICATION OF MUTANT TYPE B HUMAN ADENOVIRUS AD11 HAVING ENHANCED ONCOLYTIC POWER

摘要

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.