Evaluation of tumor-targeted systemic delivery system for oncolytic adenovirus

Abstract

Oncolytic adenovirus (oAd) in a promising strategy for cancer therapy by enhancing cancer-specific cancer cell killing, expression of transgenes along with cancer-specific viral replication as well as inducing immune responses. To overcome these limitations, we have generated oAd- conjugated with polyethylene glycol (PEG) which is directed by Trastuzumab via site-specific method (HER-PEG3.4K-oAd). HER- PEG3.4K-oAd enables effective cellular internalization due to the interaction of HER2 and anti-HER2 antibody. More importantly, systemic administration of HER-PEG3.4K-oAd showed higher tumor accumulation and lower liver sequestration than naked oAd and randomly-conjugated HER-PEG3.4K-oAd in HER2-positive cancer. These results demonstrate that HER-PEG3.4K-oAd conjugate can be a promising strategy to effectively treat HER2-overexpressing cancers through systemic administration. Graphical Abstract