Accession Number:

ADA446322

Title:

An Oncotropic Adenovirus Vector System for Breast Cancer Treatment

Descriptive Note:

Final rept. 15 Aug 2003-14 Aug 2005

Corporate Author:

ALABAMA UNIV IN BIRMINGHAM

Personal Author(s):

Report Date:

2005-09-01

Pagination or Media Count:

16.0

Abstract:

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.

Subject Categories:

  • Medicine and Medical Research
  • Microbiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE