Active Retargeting for Oncolytic Virus Delivery
Active Retargeting System
Active retargeting strategies have been employed in the delivery of a host of different types of cancer therapeutics. These techniques take advantage of cell-surface proteins that are overexpressed in tumors and use targeting ligands to target them. Incorporation of targeting ligands to the drugs produces ligand-mediated, CAR-independent binding and uptake into cells bearing appropriate receptors. A large range of proteins, antibodies and peptides can be used as mediators for active oncolytic virus retargeting, decorating the surface of the oncolytic virus, which relies on the specific interaction between the attachment proteins and the cellular receptors to lead to increased tumor recognition and specific cancer cell tropism.
Fig.1 Specificity for retargeting oncolytic viral. (Cattaneo, 2008)
Active Retargeting for Oncolytic Virus Delivery
Active retargeting of oncolytic viruses is ideal for virus therapeutic use. Retargeting oncolytic viruses for target-selective infection following intravenous delivery is challenging due to the difficulty of effectively detargeting non-target cells. Chemically couple allows for easy, efficient, and highly specific coupling of ligands, such as antibodies, proteins, or peptides, to the surface of the oncolytic virus without affecting the physical integrity of the viral particles. This active retargeting allows oncolytic viruses to bind to alternative cellular receptors and be more efficient than the native virus pathway. Retargeting with specificity to malignant tissue may enable viruses to be administered at higher doses with reduced toxicity. This retargeting can be combined with a shielding strategy to generate a truly retargeted oncolytic virus by linkage of novel ligands that enables virus retargeting through chosen receptors.
Several researchers have developed strategies for selective retargeting of oncolytic adenoviruses (Ads) with antibodies, growth vectors, or peptides. The retargeting strategies are employed whereby Ads can be designed to infect tumor cells selectively. This may be achieved by the use of binding ligands that bind both the oncolytic virus and a cell surface receptor. The covalent coating using a polymer pHPMA and retargeting strategy of incorporation of targeting ligands such as murine epidermal growth factor (mEGF), on to the polymer-coated adenoviruses can produce ligand-mediated binding and uptake into cells bearing appropriate receptors. The retargeted Ad is resistant to antibody neutralization and can infect receptor-positive target cells selectively in vitro or in vivo. Finally, the result shows that polymer-modified and retargeted Ads can infect human carcinoma cells growing as in nude mice and retain the oncolytic activity. Restricting virus tropism by physical coating, coupled with tumor-selective retargeting, has the promising to combine good anticancer efficacy with acceptable toxicity, enabling application of elevated virus doses and an improved therapeutic outcome.
The possibility of active retarget oncolytic viruses to selected receptors provides the opportunity to refine their targeted tissue tropism and their distribution kinetics in vivo. Based on our latest OncoVirapy™ platform and reliable and brilliant technical scientists, Creative Biolabs has been committed to offering world-class oncolytic virus construction and oncolytic virus engineering services to meet our customers' requirements.
Reference
- Cattaneo, R.; et al. Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded. Nature Reviews Microbiology. 2008, 6.7: 529-540.