Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan;
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Anticancer Res. 2021 Feb;41(2):773-782. doi: 10.21873/anticanres.14829.
BACKGROUND/AIM: 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.
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.
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.
These results provide important clues for the development of safe and efficient OAds.
背景/目的：溶瘤腺病毒（OAd）作为新型抗癌治疗药物引起了广泛关注。适当设计包含 E1A 基因的表达盒对于 Ad 基因组的自我复制至关重要，这对于 OAd 高效的肿瘤细胞特异性感染至关重要。已经开发了具有不同类型 E1A 基因表达盒的各种类型的溶瘤腺病毒（OAd），但其溶瘤活性和安全性特征尚未得到系统评估。在此，我们研究了五种具有不同类型 E1A 基因表达盒的 OAd 的溶瘤活性和安全性特征，以便优化 E1A 基因表达盒，开发高效、安全的 OAd。
我们制备了五种含有不同类型 E1 基因表达盒的 OAd，并检测了 OAd 的溶瘤活性和安全性特征。
在所研究的 OAd 中，具有 E1A 基因 24 个碱基缺失的 OAd-Δ24 对人肿瘤细胞系具有最高的溶瘤活性，尽管 OAd-Δ24 对正常人类细胞的细胞毒性略高于其他 OAd。
这些结果为开发安全有效的 OAd 提供了重要线索。
