目的:溶瘤腺病毒(OAds)作为一种新型的抗癌药物,已引起人们的广泛关注。包含E1A基因的表达盒的正确设计,这对于Ad基因组的自我复制是必不可少的,对于OAd的有效肿瘤细胞特异性感染至关重要。已开发出具有不同类型的E1A基因表达盒的各种类型的溶瘤腺病毒(OAds)。但尚未对其溶瘤活性和安全性进行系统评估.在本文中,我们检查了具有不同类型的E1A基因表达盒的五种类型的OAd的溶瘤活性和安全性特征,以便优化E1A基因表达盒,用于开发有效和安全的OAd。
方法:我们制备了包含不同类型E1基因表达盒的五种OAds,并检查了OAds的溶瘤活性和安全性。
结果:在所检查的OAds中,OAd-Δ24,在E1A基因中有一个24-bp的缺失,介导了对人类肿瘤细胞系最有效的溶瘤活性,尽管OAd-Δ24对正常人细胞的细胞毒性比其他OADs稍高。
结论:这些结果为开发安全有效的OAds提供了重要线索。
OBJECTIVE: Oncolytic adenoviruses (OAds) have attracted much attention as novel anticancer therapeutics. The proper design of an expression cassette containing the E1A gene, which is indispensable for self-replication of the Ad genome, is crucial for efficient tumor cell-specific infection of an OAd. Various types of oncolytic adenoviruses (OAds) possessing different types of the E1A gene expression cassettes have been developed, but their oncolytic activities and safety profiles have not been systematically evaluated. Herein we examined the oncolytic activities and safety profiles of five types of OAds possessing different types of the E1A gene expression cassette in order to optimize the E1A gene expression cassette for development of an efficient and safe OAd.
METHODS: We prepared five types of OAds containing different types of E1 gene expression cassettes, and examined the oncolytic activities and safety profiles of the OAds.
RESULTS: Among the OAds examined, OAd-Δ24, which had a 24-bp deletion in the E1A gene, mediated the most efficient oncolytic activities against the human tumor cell lines, although OAd-Δ24 showed slightly higher cytotoxicity to normal human cells than the other OAds.
CONCLUSIONS: These results provide important clues for the development of safe and efficient OAds.