Oncolytic therapy with vaccinia virus carrying IL-24 for hepatocellular carcinoma

Abstract

Abstract Background Hepatocellular carcinoma (HCC) is a highly refractory cancer associated with increasing mortality, which currently lacks effective treatment options. Interleukin-24 (IL-24) is a novel tumor suppressor cytokine that can selectively induce cancer cell apoptosis, and it has been utilized as a cancer gene therapy strategy. The vaccinia virus is a promising strategy for cancer therapy, owing to its direct viral lytic effects, as well as a vehicle to overexpress therapeutic transgenes. Methods We constructed a recombinant oncolytic vaccinia viruse (VG9-IL-24) based on vaccinia virus Guang9 (VG9) harboring the IL-24 gene. In vitro, we assessed the replication of VG9-IL-24 in HCC cell lines and normal liver cells and evaluated the cytotoxicity in different cell lines; then, we determined the expression of IL-24 by RT-PCR and ELISA. We examined apoptosis and cell cycle progression in SMMC-7721 cells treated with VG9-IL-24 by flow cytometry. In vivo, we established the SMMC-7721 xenograft mouse model to evaluate the antitumor effects of VG9-IL-24. Results In vitro, VG9-IL-24 efficiently infected HCC cell lines, but not normal liver cells, and resulted in a high level of IL-24 expression and significant cytotoxicity. Moreover, VG9-IL-24 induced an increase in the proportion of apoptotic cells and blocked the SMMC-7721 cell cycle in the G2/M phase. In vivo, tumor growth was significantly suppressed and the survival was prolonged in VG9-IL-24-treated mice. Conclusions Vaccinia virus VG9-mediated gene therapy might be an innovative treatment for cancer with tumor-specific lysis and apoptosis-inducing effects. VG9-IL-24 exhibited enhanced antitumor effects and is a promising candidate for HCC therapy.

Keywords

• Hepatocellular carcinoma
• Oncolytic vaccinia virus
• Gene therapy
• Interleukin-24
• Apoptosis