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

Abstract

Background: IL-24 (interleukin-24) is a promising, multi-functional anti-cancer agent able to selectively induce tumor cell apoptosis while sparing normal cells. Additionally, IL-24 can enhance the immune response to tumors and suppress tumor angiogenesis. In this study, we introduced IL-24 into the oncolytic adenovirus, Ad·sp·E1A((Δ24))·E1B((Δ55))·IL-24. in which E1A was engineered to target Rb (retinoblastoma) deficient or dysfunctional tumors. The survivin promoter (sp), was used to drive expression of IL-24, thereby allowing it to target most tumors. Finally, the 55 KDa gene of E1B was also deleted, thereby preventing replication in normal cells.

Results: Ad·sp·E1A((Δ24))·E1B((Δ55))·IL-24 showed enhanced antitumor effects over the E1, singly regulated oncolytic adenovirus, ONYX-015, in in vitro experiments. Furthermore, Ad·sp·E1A((Δ24))·E1B((Δ55))·IL-24 could effectively inhibit the progression of NCI-H460 lung carcinoma xenografts 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. Cell staining and western blotting for caspase activation were used to assess apoptosis. We assessed the antitumor effects of Ad·sp·E1A((Δ24))·E1B((Δ55))·IL-24 in a xenograft model.

Conclusion: This is the first study to use an E1A and E1B triple regulated oncolytic adenovirus vector carrying IL-24 to treat large tumors. We attained efficient antitumor effects both in vitro and in vivo, which provides an experimental foundation for clinical cancer therapy.