A novel Ad5/11 chimeric oncolytic adenovirus for improved glioma therapy

Abstract

Effective therapies are needed for malignant glioma patients because of the poor prognosis. Gene therapy combined with virotherapy could be the strategy of choice. In this study, we constructed a modified conditionally replicating adenoviral vector CRAd5/11-Sp-eGFP. The novel vector has the following features: i) the transduction efficiency of CRAd5 was increased using a chimeric fiber 5/11 consisting of an Ad5 tail and an Ad11 shaft and knob; ii) the tumor-specific replication of the vector was improved by utilizing the human survivin promoter to control E1 expression and a poly-A signal inserted right after the inverted terminal repeat (ITR) to stop the non-specific transcriptional activity of the ITR; iii) an expression cassette was inserted into the region between the fiber and E4 region for expressing eGFP. In vitro assays demonstrated that the novel vector could efficiently replicate and kill human glioma cells. Furthermore, CRAd5/11‑Sp-eGFP exhibited significantly increased antitumor effects compared with the control adenoviruses in a xenograft model of glioma. Our results indicate that CRAd5/11-Sp-eGFP represents a promising candidate drug in the treatment of malignant gliomas.