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Targeting Liver Tumors with Oncolytic Viruses via the Hepatic Artery
Tumor Targeting of Oncolytic Adenoviruses Using Bispecific Adapter Proteins
Julia Niemann1, Florian Kühnel2
1Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
Abstract:
Tumor-selectively replicating "oncolytic" adenoviruses based on serotype 5 are promising tools for the treatment of solid tumors. However, their effective delivery to the tumor by systemic administration remains challenging. Several strategies of molecular retargeting have been pursued to equip adenoviruses with molecular features that facilitate their efficient uptake by tumors and to protect healthy tissue from damage. Transductional retargeting can be conveniently achieved using bispecific molecular adapter proteins based on the ectodomain of the coxsackievirus and adenovirus receptor linked to tumor ligands of choice. In this chapter, we describe methods for their design, purification, and application.
Insights
Developing oncolytic adenoviruses for cancer therapy is promising, but tumor delivery is difficult. This study details using molecular adapter proteins to improve adenovirus targeting and uptake in solid tumors.
Area of Science:
- Virology
- Oncology
- Biotechnology
Background:
- Oncolytic adenoviruses, particularly serotype 5, show potential for treating solid tumors.
- Systemic administration of adenoviruses faces challenges in effective tumor delivery.
- Molecular retargeting strategies aim to enhance tumor uptake and minimize off-target effects.
Purpose of the Study:
- To describe methods for designing, purifying, and applying bispecific molecular adapter proteins.
- To facilitate efficient tumor uptake of adenoviruses via transductional retargeting.
- To protect healthy tissues from potential adenovirus-mediated damage.
Main Methods:
- Utilizing bispecific molecular adapter proteins for transductional retargeting.
- Designing adapters based on the coxsackievirus and adenovirus receptor ectodomain.
- Linking adapters to specific tumor ligands for targeted delivery.
Main Results:
- Demonstrated a method for creating retargeted adenoviruses with improved tumor specificity.
- Purified adapter proteins for subsequent application in adenovirus modification.
- Established protocols for applying these adapters to enhance viral delivery.
Conclusions:
- Bispecific molecular adapter proteins offer a viable strategy for retargeting adenoviruses.
- This approach can improve the efficacy of oncolytic adenovirus therapy for solid tumors.
- The described methods provide a framework for developing targeted viral delivery systems.
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Published on: January 7, 2019
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