Evolution of oncolytic adenovirus for cancer treatment

Oncolytic adenovirus (Ad) has been used in cancer gene therapy largely due to its ability to selectively infect and replicate in tumor cells. However, because the oncolytic antitumor activity is insufficient to effectively eliminate tumors, various strategies have been devised to improve the therapeutic efficacy. Single-vector Ads “armed” with short hairpin RNA, cytokines, or matrix-modulating proteins have been developed. Two clear advantages are viral amplification of the therapeutic gene, and the additive effects of oncolytic and therapeutic gene-mediated antitumor activities. To develop systemically injectable Ad carriers, strategies to modify the Ad surface with polymers, liposomes, or nanoparticles have been shown to extend circulation time, reduce immunogenicity, and result in increased antitumor effect as well as lower accumulation and toxicity in liver. Specific targeting platforms for tumor-selective oncolytic therapies against both primary and metastatic cancers have been developed. This review will focus on updated strategies to develop potent oncolytic Ads for use in cancer treatment.