Gene Therapy of Disseminated Breast Cancer Using Adenoviral Vectors Targeted Through Immunological Methods
Abstract
Targeting of adenovirus 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 infection 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 on a large scale to an anti-EGFR antibody (425) and an anti-erbB-2R antibody (Herceptin) to yield Fab-425 and Fab-Herceptin conjugates, respectively. These conjugates were used to target adenovirus specifically to E()F and erbB-2 receptors on BT-474, MDA-MB-468, MDA-MB-134, MDA-MB-231, MDA-MBA-453, and SK-BR-3 breast cancer cells. In addition, the conjugates could specifically target adenovirus to the receptors in a hetergeneous cell population. Preliminary in vivo studies were conducted which will be valuable for future evaluation of the conjugates. Also, studies using an adenovirus encoding for a therapeutic gene were evaluated. These results are significant in that they demonstrate that adenovirus vectors can be specifically delivered to breast cancer cells in a heterogeneous cell population. This will be significant for treating disseminated breast cancer with adenovirus vectors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA381175
Entities
People
- Buck E. Rogers
Organizations
- University of Alabama