An Oncotropic Adenovirus Vector System for Breast Cancer Treatment
Abstract
In this study, we generated the replicating Ad5-based vector encoding the Ad4l short fiber devoid of CAR and HSG binding while containing C-terminal His tag for targeting purposes. We compared our Ad5F4ls6H vector with control Ad5F4ls for the ability to induce cytopathic effect in CAR-positive 293 cells. We found that the parental 293 cells were relatively refractory to Ad5F4ls6H while it was significantly more infectious in 293AR cells, expressing the cognate artificial anti-His tag receptor, as compared to the control Ad5F4ls vector. These results suggest that generated Ad5F4ls6H indeed lacks CAR-mediated tropism while is able to utilize fiber-incorporated His tag for cell binding. In parallel, we produced bispecific 3D5-C6.5 scFv molecule with affinities for both His tag and c-erbB-2 oncoprotein. We then examined the utility of the 3D5-C6.5 adapter for Ad5F4ls6H vector targeting by assessing the improvements in oncolysis of c-erbB-2-positive cells. The presence of the c-erbB-2-targeting 3D5-C6.5 adapter in the infection medium significantly improved the oncolytic potency of the AdSF4ls6H vector in c-erbB-2-positive 435.eBl breast cancer cells. These results indicated that the 3D5-C6.5 adapter mediated specific Ad5F4ls6H binding to the cellular c-erbB-2-oncoprotein allowing efficient oncolytic infection and, thus, demonstrated the feasibility of our Ad targeting approach in vitro.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA430028
Entities
People
- Igor P. Dmitriev
Organizations
- University of Alabama