Combination therapy with F5/35 fiber chimeric conditionally replicative adenoviruses expressing IL‐24 enhances the antitumor effect of temozolomide against melanoma

作者：Ming Yang, Chunsheng Yang, Yingkai Tao, Jianqin Tang, Qian Huang, Wenwen Guo, Shou-Xin Feng, Aijun Jiang, Xifeng Xu, Guan Jiang, Yan Liu · 发表于：Cancer Medicine · 年份：2018 · DOI：10.1002/cam4.1843 · 被引用次数：11 · 研究领域：Virus-based gene therapy research、CAR-T cell therapy research、Cytokine Signaling Pathways and Interactions

BACKGROUND: Temozolomide (TMZ) is widely used to treat melanoma; however, response rates to TMZ are low because of rapid and frequent resistance. Conditionally, replicative adenoviruses (CRAds) are an effective and promising approach. The receptor for adenovirus is coxsackie-adenovirus receptor (CAR), which is poorly expressed in most cells. However, CD46, which is the receptor of species B adenoviruses (Ads), is highly expressed in many cells. METHODS: We constructed CRAd F5/35-ZD55-IL-24, which uses the viral receptors CAR and CD46 for entry into cells. We investigated the antitumor effect of F5/35-ZD55-IL-24 in combination with TMZ to treat melanoma in vitro and in vivo. RESULTS: The \results indicated that F5/35-ZD55-IL-24 in combination with TMZ produced additive or synergistic antitumor and pro-apoptotic effects in melanoma cells. The combination of F5/35-ZD55-IL-24 and TMZ significantly inhibited the growth of melanoma in vivo. In addition, the antitumor effect of F5/35-ZD55-IL-24 was superior to that of ZD55-IL-24 and ZD55-IL-24 combined with TMZ. CONCLUSIONS: The use of F5/35-ZD55-IL-24 in conjunction with TMZ is a promising approach for anti-melanoma therapy. Our results indicated that F5/35-ZD55-IL-24 in combination with TMZ produced additive or synergistic antitumor effect and pro-apoptotic effect in melanoma cells highly expressed CD46. The combination of F5/35-ZD55-IL-24 and TMZ significantly inhibited the growth of melanoma in vivo. We also found the antitumor ...