Targeted Gene Delivery to Accomplish Gene Therapy for Breast Cancer

摘要

We are developing methods to derive gene transfer vectors capable of accomplishing targeted gene delivery to metastatic breast cancer cells. In this regard, strategies have been explored to modify adenoviral vectors by altering their binding tropism. Genetic methods employed have allowed for the modification of the native adenoviral binding protein (fiber) to incorporate cancer-relevant cell-binding ligands. Immunologic methods have yielded an antifiber antibody which specifically ablates native adenoviral tropism and provides a site for the addition of breast cancer-relevant ligands. The results developed herein have allowed for the successful retargeting of the adenoviral vector via either the genetic or immunologic approach. In addition, targeted, tumor-specific gene delivery has been achieved in vitro. These methods will now allow the evaluation of these vector systems in vivo models of human breast cancer. The-utility of the vectors in this context will allow the development of gene therapy strategies for disseminated breast cancer.