[Advances in research on oncolytic adenoviruses in tumor therapy]

Area of Science:

• Oncolytic virotherapy
• Gene therapy
• Cancer treatment

Context:

• Oncolytic adenoviruses (Ads) are utilized in tumor therapy for their ability to selectively replicate in and lyse cancer cells.
• Human tumor complexity and mutability necessitate improvements in the selectivity, efficacy, and safety of oncolytic Ads.

Purpose:

• To review strategies for enhancing the performance of oncolytic adenoviruses in cancer therapy.
• To highlight advancements in engineering oncolytic Ads for improved tumor targeting and reduced toxicity.

Summary:

• Oncolytic Ads engineered to express therapeutic payloads like short hairpin RNA, cytokines, suicide genes, or matrix-modulating proteins exhibit superior antitumor activity compared to wild-type viruses.
• Tumor-specific promoters, such as hTERT and HRE, significantly enhance the selectivity of oncolytic Ads for cancer cells.
• Surface modifications of oncolytic Ads with polyethylene glycol (PEG), liposomes, nanoparticles, or polypeptides reduce immunogenicity and hepatotoxicity, while systemic administration benefits from PEGylation linked to targeting moieties like antibodies or ligands, further increasing selectivity.

Impact:

• Engineered oncolytic Ads represent a promising approach to targeted virotherapy by integrating viral and non-viral vector advantages with immunotherapy.
• These advancements hold potential for more effective and safer cancer treatments through enhanced virotherapy strategies.