CHE 598 Seminar: Engineering Viruses for Therapeutic Use

About the event

Presenter: Ching-An Peng, Chair & Professor, Department of Chemical & Biological Engineering, University of Idaho

Although several trials showed significant shrinkage when viruses were injected directly into tumor nodules, systemic intravenous delivery of virotherapeutics is required for the treatment of metastatic cancers. This presents a challenge, because viruses could be rapidly cleared from the blood circulation via the host immune system before they reach tumor sites. To be effective, therapeutic viruses for intravenous delivery need to possess adequate stability in blood to selectively target cancer cells and elicit tumor oncolysis. In this study, we harnessed CD47’s antiphagocytic and CD200’s anti-inflammatory characteristics to functionalize viruses and then loaded onto macrophages to explore the potential use of such biomimetic viruses for gene delivery. Our results showed that nano-sized viral particles decorated with CD47-CD200 fusion protein decreased phagocytosis activities of macrophages. Such diminution of phagocytosis was examined to be associated with (1) CD47-SIRPα interaction and (2) downregulation of Toll-like receptor 4 expression on the surface of macrophages. Moreover, J774A.1 macrophages treated with CD47-CD200-tethered viruses decreased the secretion of pro-inflammatory cytokines.