Advances in research on oncolytic adenoviruses in tumor therapy / 病毒学报

ABSTRACT

Oncolytic adenoviruses (Ads), which are live, replication-competent viruses that can selectively replicate in tumor cells and lead to cell lysis, have been used in tumor therapy. But due to the complexity and high mutability of human tumors, it becomes a major strategy to improve the selectivity, efficacy, and safety of oncolytic Ads. The oncolytic Ads that can express short hairpin RNA, cytokines, suicide gene, and matrix-modulating proteins have higher antitumor activity than the wild type. Tumor-specific promoters, especially hTERT and HRE promoters, increase the selectivity of oncolytic Ads for tumor cells. Moreover, oncolytic Ads surface-modified by polyethylene glycol (PEG), liposomes, biodegradable nanoparticles, and polypeptides have reduced immunogenicity and hepatotoxicity and improved antitumor activity when systemically administered, and the selectivity of oncolytic Ads can be significantly increased when linking PEG to antibodies, small peptides, cytokines, and ligands. Therefore, engineered oncolytic Ads combining the advantages of viral and non-viral vectors, as well as immunotherapy, are a promising strategy for improving the efficacy of targeted virotherapy.