The antitumor efficacy of IL-24 mediated by E1A and E1B triple regulated oncolytic adenovirus

Abstract

Background: IL-24 (interleukin-24) is a promising multifunctional anticancer agent with the ability of selectively inducing tumor cell apoptosis while sparing normal cells. Besides, IL-24 can enhance immune response to tumor and suppress tumor angiogenesis. In this study, we introduced IL-24 into the triple regulated oncolytic adenovirus, Ad·sp·E1A (Δ24)·E1B(Δ55)•IL-24, in which E1A was deleted 24 bp (from 923 bp to 946 bp) to target Rb (retinoblastoma) deficient or dysfunctional tumors and driven by survivin promoter (sp) to target almost all tumors, and the E1B was deleted its 55 KDa gene. Results: Ad·sp·E1A(Δ24)·E1B (Δ55)·IL-24 exhibited much better antitumor effect than E1 single regulated oncolytic adenovirus ONYX-015 in vitro experiments. Furthermore, Ad·sp·E1A(Δ24)·E1B (Δ55)·IL-24 could effectively inhibit the progression of the NCI-H460 xenograft lung carcinoma in nude mice. Methods: The antitumor effect of Ad·sp·E1A(Δ24)·E1B (Δ55)·IL-24 was assessed by MTT assay and crystal violet staining in a panel of tumor cells. Apoptotic cell staining and western blot analysis were performed to observe morpholgical changes of tumor cells and detect the changes of some proteins in caspase pathway. Moreover, the antitumor effect of Ad·sp·E1A(Δ24)·E1B (Δ55)·IL-24 in nude mice was assessed for big tumor size. Conclusion: This study firstly used the E1A and E1B triple regulated oncolytic adenovirus vector carrying IL-24 to treat large tumors and attained efficient antitumor effect both in vitro and in vivo, which provides an experimental foundation for clinical cancer therapy. © 2010 Landes Bioscience.