Gene Therapy of Disseminated Breast Cancer Using Adenoviral Vectors Targeted Through Immunological Methods
Abstract
Targeting of adenovirus (Ad) vectors, encoding for therapeutic genes, to tumor-specific receptors on breast cancer cells should result in specific killing of these cells. Targeting is necessary to prevent gene transfer in normal tissues resulting from the wide array of normal cells by adenovirus. We have previously reported the use of an anti-knob antibody fragment (Fab), which prevents Ad infection, conjugated to folate to target adenovirus to folate receptor positive cells. In this report, the Fab has been conjugated to FGF2, EGF, and an anti-erbB-2 antibody to yield Fab-FGF2, Fab-EGF, and Fab-erbB2 conjugates, respectively. These conjugated were used to target an adenovirus encoding the firefly luciferase gene AdCMVLuc) to FGF, EGF, and erbB-2 receptors on BT-474, MDA-MB-468, MDA-MB- 134, MDA-MB-231, MDA-MB-453, and SK-BR-3 breast cancer cells. Also, live-cell binding assays with radio labeled Ad, FGF2, EGF, and anti-erbB-2 antibody were performed to determine relative receptor expression. These data suggest that there is a relationship between the level of receptor expression and gene transfer. Also, in many instances the targeted adenovirus yielded better gene transfer than adenovirus alone. In this regard, use of the Fab-FGF2 conjugate resulted in the best gene transfer in the BT-474, MDA-MB-134, and MDA-MB-231 cells, the Fab-EGF was best in the MDA-MB-468 and SK-BR-3 cells and the Fab-erbB-2 was best in the MDA-MB-453 cells. These results are significant in that they demonstrate that Ad vectors can be 5 specifically delivered to breast cancer cells and result in enhanced gene transfer. This will be significant or treating disseminated breast cancer with with AD vectors enhance gene transfer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADB244250
Entities
People
- Buck E. Rogers
Organizations
- University of Alabama