Tumor Targeting of Oncolytic Adenoviruses Using Bispecific Adapter Proteins

• Published in: Methods in molecular biology (Clifton, N.J.) Vol. 2058; p. 31
• Main Authors: Niemann, Julia, Kühnel, Florian
• Format: Journal Article
• Language: English
• Published: United States 01.01.2020
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adenoviridae - genetics; Animals; Disease Models, Animal; Genetic Therapy - methods; Genetic Vectors - genetics; Humans; Neoplasms - etiology; Neoplasms - pathology; Neoplasms - therapy; Oncolytic Virotherapy - methods; Oncolytic Viruses - genetics; Soluble CAR; Bispecific adapter proteins; Tumor targeting; Hepatic detargeting; Oncolytic adenovirus
• ISSN: 1940-6029
• DOI: 10.1007/978-1-4939-9794-7_3

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.