A novel capsid-modified oncolytic recombinant adenovirus type 5 for tumor-targeting gene therapy by intravenous route

Area of Science:

• Oncolytic virotherapy
• Gene therapy
• Molecular oncology

Background:

• Oncolytic adenovirus (Ad)-vectored gene therapy shows promise for cancer treatment.
• Limited cancer cell selectivity and tumor specificity of Ads restrict intravenous (IV) application.

Purpose of the Study:

• To engineer novel Ad5 vectors with enhanced tumor targeting and anti-cancer efficacy for IV administration.
• To improve cancer cell selectivity by modifying viral capsid proteins.

Main Methods:

• Constructed recombinant Ad5 vectors with capsid protein IX modified by tumor necrosis factor related apoptosis-inducing ligand (TRAIL) using leucine zipper domains.
• Analyzed the presence and function of TRAIL on purified virus particles (rAd5pz-zTRAIL-RFP).
• Developed a novel modified oncolytic Ad (rAd5pz-zTRAIL-RFP-SΔ24E1a) and evaluated its anti-tumor effects and biodistribution in vitro and in vivo.

Main Results:

• Modified Ads displayed TRAIL on their surface, inducing cancer cell apoptosis before foreign gene expression.
• The novel rAd5pz-zTRAIL-RFP-SΔ24E1a demonstrated significantly enhanced in vitro and in vivo anti-tumor effects.
• This modified Ad exhibited improved tumor tissue targeting and reduced liver tropism upon IV injection.

Conclusions:

• Successfully developed new oncolytic Ad5 gene therapy vectors with enhanced targeting and efficacy.
• The engineered Ads provide a viable platform for clinical applications in cancer treatment.
• TRAIL linkage to the viral capsid significantly boosts anti-tumor activity and tumor specificity.