Targeting of Adenovirus Vectors to Breast Cancer Mediated by soluble Receptor-Ligand Fusion Proteins

摘要

Breast cancer is the most common cancer in women worldwide and continues to be a major health problem. It accounts for one-third of cancer diagnoses and 15% of cancer deaths in U.S. This argues strongly for the development of effective strategies to accomplish treatment of breast cancer. Cancer gene therapy has been evaluated as a candidate therapy for a variety of carcinomas to eradicate loco-regional and disseminated disease, which is not adequately addressed by conventional treatments. Viral agents could represent a powerful anticancer treatment platform if they can be designed to infect tumor cells with a requisite level of efficiency and specificity. In this regard, replication-competent adenovirus (Ad) vectors have been of high interest, owing to their ability to propagate in epithelial cells, the origin of most human cancers. However, realization of the full potential of Ad vectors for targeted cancer treatment is currently limited by broad viral tropism which results in widespread tissue distribution of systemically administered Ad with preferential accumulation in the liver (1). Several studies, including our own work, have established the feasibility of tropism modification of Ad vectors for cell-specific gene delivery (2-6). The distinct aim of the current study was to evaluate the potential for such targeting approaches to maintain specificity in the stringent context of systemic vascular administration. Such a demonstration would be a key milestone for the development of targeted Ad vectors for gene therapy and have important implications for treatment of carcinoma of the breast.