Treatment of Primary and Metastatic Breast Cancer by an Armed Replicating Adenoviral Vector.

摘要

In this Exploration Award, we were testing the concept that an oncolytic adenovirus armed with the osteoprotegerin (OPG) gene would be able to eradicate a primary breast cancer tumor by oncolysis, and that secretion of OPG from the infected and lysed cells into the systemic circulation would inhibit osteolytic bone metastases of the breast cancer. We have constructed a replication-defective adenoviral vector expressing human OPG fused with the Fc domain of human IgG, and have evaluated the efficacy of the armed replicating adenoviral vector in vitro. We have demonstrated that sCAR-ligand fusion proteins targeted to CEA, erbB-2 and the EGFR can mediate CAR-independent adenoviral infection of MDA-MB-231 breast cancer cells. These studies provided preliminary data for a funded NIH R01 grant to develop an armed replicating adenovirus for the treatment of bone metastases of breast cancer. To this end, we hypothesize that a replication-selective adenovirus armed with OPG would eradicate bone metastases of breast cancer both directly, by oncolysis, and indirectly, by inhibiting osteoclastic bone resorption and thus reducing the tumor burden.