Oncotropic Adenovirus Vector System for Breast Cancer Treatment

摘要

In this study, we generated the replicating Ad5-based vector encoding the Ad41 short fiber devoid of CAR and HSG binding while containing C- terminal His tag for targeting purposes. We produced bispecific 3D5-C6.5 scFv with affinities for both His tag and c-erbB-2 oncoprotein. The utility of the 3D5-C6.5 adapter for Ad5F41s6H vector targeting was assessed in c-erbB-2- positive cells. Ad5F41s6HsFv and Ad5F41sFv vectors that express the secretory 3D5-C6.5 adapter upon cell infection have been rescued and efficiently propagated while several attempts to rescue their derivatives lacking integrin- dependent cell binding were unsuccessful. The improved capacity of Ad5F41 s6HsFv vector producing 3D5-C6.5 to achieve infection of c- erbB-2-positive cells was demonstrated by the analysis of Ad replication in vitro. However, Ad5F41 s6HsFv vector has not demonstrated appreciable changes in the in vivo distribution profile compared to Ad5FY477A-6H and Ad5 vectors indicating that additional ablation of integrin-binding is required to retarget Ad vector from normal tissue to the tumor site upon systemic administration.